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654 




§3 SCIENTIFIC LIBRARY | 




GPO 16—53001-1 



THE 



american 
Journal of Pharmacy 



PUBLISHED BY AUTHORITY OF THE 2?- 



PHILADELPHIA COLLEGE OF PHARMACY 



EDITED BY 



HENRY KRAEMER 



PUBLICATION COMMITTEE FOR IQH 

SAMUEL P. SADTLER M. L WILBERT 

JOSEPH W. ENGLAND FLORENCE YAPLE 

JOSEPH P. REMINGTON CHARLES H. LaWALL 

AND TH£ "EDITOR 



'•'y,A>. VOLUME 8j>,-/; v> 



PHILADELPHIA 
1911 



( O n r ^ 



/ 




Ai^ T Ph.] 



9 



[December, 191 1 



DISTILLED WATER 

AT 

2 Gents per Gallon 

stokes Automatic Gas-tieated Water 
Still is guaranteed to do this 

Price only $18.00 

WRITE FOR CIRCULAR A-I TO 



F. J. STOKES MACHINE CO. 

17tli and Cambria Streets Philadelphia 



ESSENTIAL OILS 

PURITY Standard of QUALITY 



FRITZSCHE BROTHERS 

NEW YORK 



Brancti of SCHIMMBL & CO. 

Germans^ 

Kounded " 1829 



POL LAN TI N for Hay Fever 




Am. J. Vh.] lo [December, i 



SECRETARIES OF BOARDS OF PHARMACY 



State. 


Name of Secretary. 


Address. 


Alabama, 


E. P. Gait, 


Selma. 


Arizona, 


A. G. Hulett, 


Phcenix. 


Arkansas, 


J. F. Dowdy, 


Little Rock. 


California, 


Louis Zeh, 


San Francisco. 


Colorado, 


S. L. Bresler, 


Denver. 


Connecticut, 


J. A. Leverty, 


Bridgeport. 


Delaware, 


Albert Doughert}'^, 


Wilmington. 


District of Columbia, 


S. L. Hilton, 


Washington. 


Florida, 


D. W. Ramsaur, 


Palatka. 


Georgia, 


C. D. Jordan, 


Monticello. 


Idaho, 


T. M. Starrh, 


Shoshone. 


Illinois, 


F. C. Dodds, 


Springfield. 


Indiana, 


W. H. Rudder, 


Salem. 


Indian Territory, 


H. D. Knisely, 


Checotah. 


Iowa, 


E. J. Moore, 


Des Moines. 


Kansas, 


W. E. Sherriff, 


Ellsworth. 


Kentucky, 


J. W. Gayle, 


Frankfort. 


Louisiana, 


F. A. Earhart, 


New Orleans. 


Maine, 


F. W. Buckman, 


Showhegan. 


Maryland, 


Ephraim Bacon, 


Roland Park. 


Massachusetts, 


P. J. McCormick, 


Boston. 


Michigan, 


E. J. Rodgers, 


Port Huron. 


Minnesota, 


C. T. Heller, 


St. Paul. 


Mississippi, 


L. H. Wilkinson, 


Greenwood. 


Missouri 


C. E. Zinn, 


Kansas City. 


Montana, 


T. M. Kehoe, 


Billings. 


Nebraska, 


A. V. Pease, 


Fairbury. 


Nevada, 


R. L. Prouty, 


Tonopah. 


New Hampshire, 


F. H. Wingate, 


Nashua. 


New Jersey, 


H. A. Jorden, 


Bridgeton. 


New Mexico, 


A. J. Fischer, 


Santa Fe. 


New York, 


W. L. Bradt, 


Albany. 


North Carolina, 


F. W. Hancock, 


Oxford. 


North Dakota, 


W. S. Parker, 


Lisbon. 


Ohio, 


F. H. Frost, 


Columbus. 


Oklahoma, 


J. C. Burton, 


Stroud. 


Oregon, 


C. J. Huntley, 


Oregon City. 


Pennsylvania, 


L. L. Walton, 


Williamsport. 


Rhode Island, 


J. E. Brennan, 


Pawtucket. 


South Carolina, 


F. M. Smith, 


Charleston. 


South Dakota, 


E. C. Bent, 


Dell Rapids. 


Tennessee, 


Ira B. Clark, 


Nashville. 


Texas, 


R. H. Walker, 


Gonzales. 


Utah, 


W. H. Dayton, 


Salt Lake. 


Vermont, 


D. F. Davis, 


Barre. 


Virginia, 


T. A. Miller, 


Richmond. 


Washington, 


P. Jensen, 


Tacoma. 


West Virginia, 


A. Walker, 


Sutton. 


Wisconsin, 


Edward Williams, 


Madison. 


Wyoming, 


C .B. Gunnell, 


Evanston, 



DR. SUSAN HAYHURST, 1820 



THE AMERICAN 



JOURNAL OF PHARMACY 

B '^-^ ^ ^ 

JANUARY, /p/^^, ^' 

% % v,^ 

THE CONSTITUENTS OF THE RHIZQME OF IRIS 
VERSICOLOR. 

By Frederick B. Power and Arthur H. Salway, 
A Contribution from the Wellcome Chemical Research Laboratories, London. 

The rhizome and roots of Iris versicolor, Linne (Nat. ord. Iri- 
dacece) , commonly known as the ''Larger Blue Flag," were recognized 
for several decades by the Pharmacopoeia of the United States (Re- 
visions of 1870, 1880 and 1890) under the official title of Iris, 
together with liquid and solid extracts prepared therefrom. In the 
eighth revision (1900), however, of the above-mentioned work the 
drug was deleted, probably on account of its limited use or the varia- 
bility and uncertainty of its action. Under the names of " Irisin " 
or Iridin " preparations have been introduced, and are still some- 
what employed medicinally, which consist either of the resin or of 
an ethereal or alcoholic extract of the drug. 

Although in the literature ^ it has been recorded that the rhizome 
of Iris versicolor contains starch, gum, tannin, sugar, an acid resin, 
and fatty oil, together with some volatile matter and possibly an 
alkaloid, its constituents have never been thoroughly investigated. 
As the rhizome, at least in the fresh state, evidently possesses con- 
siderable potency, acting as a cathartic and emetic, although its 
medicinal activity is stated to become impaired by age, it was 
deemed desirable to subject it to a complete chemical examination. 

EXPERIMENTAL. 

The material employed for the present investigation consisted of 
commercial " Blue Flag Root," the identity of which was estal3lished, 
and it appeared to be of good quality. 

As a preliminary experiment, a small portion of the ground 



^This Journal, 1876, 48, p. 406; 1881, 53, p. 601; 1884, 56, p. 616, 

(I) 



2 



Rhizome of Iris Versicolor. 



f Am. Jour. Pharm. 
t January, 1911. 



material was tested for the presence of an alkaloid, but with a nega- 
tive result. A further quantity (25 grammes) of the ground 
material was successively extracted in a Soxhlet apparatus with 
various solvents, when the following amounts of extract, dried at 
100°, were obtained: 



Petroleum (b. p. 


35-50°) extracted 0.30 Gm. 


= 1.2 per cent. 


Ether 


0.80 " 


= 3-2 " " 


Chloroform 


0.22 " 


= 0.9 " " 


Ethyl acetate 


" 042 " 


= 17 " " 


Alcohol 


" 4.13 " 


= 16.5 



Total 5.87 Gm. = 23.5 per cent. 

For the purpose of a complete examination 62.82 kilogrammes 
of the ground material were extracted by continuous percolation 
with hot alcohol. After removing the greater portion of the alcohol, 
there remained a viscid, dark-colored extract, amounting to 15.72 
kilogrammes. 

Distillation of the Extract with Steam. Separation of an 
Essential Oil. 

Two kilogrammes of the above-mentioned alcoholic extract were 
mixed with a little water, and subjected to distillation in a current 
of steam for several hours. The distillate contained a small quantity 
of oil floating on the surface, which was extracted with ether. The 
ethereal liquid was dried, and the solvent removed, when there re- 
mained 2 grammes of an essential oil, this amount corresponding to 
0.025 per cent, of the weight of the drug. The essential oil possessed 
a yellow color, a strong, somewhat unpleasant odor, and contained 
traces of furfuraldehyde, as indicated by the aniline color test. Its 
density was 0.9410 at 20°/20° ; when examined polarimetrically, 
no appreciable optical rotation could be observed. 

Non-volatile Constituents of the Extract. 

After removal of the essential oil, as above described, there re- 
mained in the distillation flask a deep brown, aqueous liquid (A) and 
a brown resin (B). These were separated by filtration, and the 
resin well washed with water, the washings being added to the main 
portion of the aqueous liquid. 



Am. Jour. Pharm. » 
January, 1911. j 



Rhizome of Iris Versicolor. 



3 



Examination of the Aqueous Liquid (A), 

The aqueous liquid was concentrated to a convenient volume 
under diminished pressure, and then repeatedly extracted with ether, 
the ethereal extracts being united, washed with a little water, and 
dried with anhydrous sodium sulphate. On removing the solvent, 
15 grammes of an oily residue were obtained, which did not solidify 
on keeping. For the further examination of this product it was 
redissolved in ether, and the ethereal liquid shaken successively with 
solutions of ammonium carbonate (a), sodium carbonate (b) , and 
sodium hydroxide (c). 

Isolation of isoPhthaUc Acid, C6H4(C02H)2. 
The ammonium carbonate extract (a) of the above-mentioned, 
ethereal liquid was acidified with dilute sulphuric acid, when an oil 
was precipitated which was taken up by ether. This ethereal solution 
was then washed, dried, and the solvent removed, when 10.5 
grammes of a brown, viscid oil remained. The latter was next 
heated with methyl alcohol in a current of dry hydrochloric acid gas, 
and thus converted into its methyl ester, which, by treatment with 
dilute, aqueous sodium hydroxide could be separated into phenolic 
and non-phenolic portions. The portion insoluble in alkali, compris- 
ing the non-phenolic esters, amounted to 7 grammes. It distilled at 
1 40-260 °/20 mm., the greater portion, however, passing over at 
i50-i8o°/2O mm. This ester was then converted into the corre- 
sponding acid by heating for a short time with alcoholic potassium 
hydroxide. After hydrolysis was complete, the alcohol was re- 
moved, and the alkaline liquid acidified with dilute sulphuric acid, 
when a semi-solid, oily product was precipitated. The latter was re- 
moved by filtration, dried on a porous tile, and purified by crystal- 
lization from dilute alcohol. It was thus obtained in colorless, glis- 
tening leaflets, which did not melt below 300°. 

0.0919 required for neutralization 10.85 ^.c. Ba(OH)2. 

Neutralization value = 66.2 
C(.H^(CO.M).^ requires Neutralization value = 66.8 
The crystalline acid, above described, was only sparingly soluble 
in hot water, but readily soluble in alcohol. When heated strongly 
in an ignition tube, it sublimed, forming colorless prisms on the 
cooler portions of the tube. Its barium salt was readily soluble in 



4 



Rhizome of Iris Versicolor. 



f Am. Jour. Pharm. 
I Jaiuiiuy, 1911. 



water. These properties, together with the resuh of its titration, as 
given above, indicated it to be Wfphthahc acid. In order to con- 
firm its identity, a portion of the substance was heated with phos- 
phorus pentachloride in the presence of benzene, and the product 
vigorously agitated with concentrated ammonia. In this manner an 
acid amide was formed, which was collected and well washed with 
water. The latter compound sintered at 260° and melted completely 
at 275°. A known specimen of uophthalic acid, when similarly 
treated, also yielded an acid amide sintering at 260° and melting 
at 275°, and when the two specimens of amide were mixed the melt- 
ing point remained unaltered. 

The above-described substance was thus identified as z^ophthalic 
acid, the occurrence of which in nature does not appear to have been 
hitherto observed. The amount of this acid obtained from 2 kilo- 
grammes of the alcoholic extract of " Blue Flag Root " was about 
0.15 gramme, thus corresponding to 0.0019 per cent, of the weight 
of the drug. 

The phenolic methyl esters, which had been separated from 
the non-phenolic portion by means of sodium hydroxide, as above 
described, were hydrolyzed by heating for a short time with an 
aqueous solution of this alkali. The liquid was then acidified, when 
a resinous precipitate was deposited, which was extracted with ether. 
The ethereal liquid was washed and dried, and, on removing the 
solvent, yielded about 1 gramme of a brown oil. Since the latter 
did not show any indication of crystallizing, it was agitated with 
light petroleum, the petroleum extract decanted from insoluble oil, 
and the solvent allowed to evaporate. A trace of a crystalline solid 
was thus obtained, which gave a violet coloration with ferric chloride 
as well as the characteristic odor of oil of wintergreen when heated 
with methyl alcohol and a few drops of concentrated sulphuric acid. 
The presence of salicylic acid was thus indicated, but the amount 
was too small to admit of complete identification. That portion of 
the oil which was insoluble in light petroleum was again converted 
into its methyl ester, and the latter benzoylated by the Schotten-Bau- 
mann method. The product was oily, but gradually deposited a 
few colorless crystals. These were separated from adhering oil 
by spreading them on a porous tile, and then recrystallized from alco- 
hol, when they separated in stellar aggregates of fine needles, melting 



Am. Jour. Pharm. ) 
January, 1911. ) 



Rhizome of Iris Versicolor. 



5 



at iio°. The amount of this substance was too small for further 
examination. 

The sodium carbonate {h) and the sodium hydroxide {c) ex- 
tracts of the original ethereal liquid, when acidified, yielded only 
small quantities of gummy substances from which no definite com- 
pound could be isolated. On finally evaporating the ethereal liquids, 
which had thus been completely extracted with alkalies, 1.5 grammes 
of a yellow, amorphous mass remained. 

The original aqueous liquid (A), which had been extracted with 
ether as above described-, was next repeatedly shaken with amyl 
alcohol. The united amyl alcoholic extracts were washed with 
water, and then extracted successively with aqueous solutions of am- 
monium carbonate, sodium carbonate, and sodium hydroxide. The 
ammonium carbonate extract, when acidified with dilute sulphuric 
acid, yielded a resinous precipitate, which was taken up by amyl 
alcohol, the solution being washed, dried, and the solvent removed. 
The brown syrup thus obtained, which showed no tendency to 
crystallize, gave an intense black coloration with ferric chloride, and 
evidently contained tannin. For the further examination of this 
syrup it was esterified, but no definite substance could be isolated by 
this treatment. 

The sodium carbonate and sodium hydroxide extracts of the amyl 
alcoholic liquid yielded only small quantities of brown, amorphous 
resins, which were specially examined for glucosides, but no positive 
evidence of the presence of such compounds was afforded. The 
amyl alcoholic liquid, which had been extracted with the various 
alkalies, was finally washed, and the solvent removed under dimin- 
ished pressure. A thick, gummy mass, amounting to about 2 
grammes, was thus obtained, but no crystalline compound could be 
isolated from it. 

The aqueous liquid which had been extracted with ether and 
with amyl alcohol, as above described, was dark brown in color, 
and gave a copious brown precipitate on the addition of a slight 
excess of basic lead acetate. The lead precipitate was collected, 
thoroughly washed, then suspended in water, and decomposed by 
hydrogen sulphide. After removing the lead sulphide by filtration, 
the filtrate was concentrated under diminished pressure to a small 
volume. The concentrated licjuid was light yellow, gave a faint 
brown coloration with ferric chloride, and, after standing for some 



6 



Rhizoinc of Iris Versicolor. 



( Am. Jour. Pharm. 
\ January, 1911. 



time, deposited a brown, amorphous solid, but nothing crystalline 
was obtained from it. 

The filtrate from the basic lead acetate precipitate, after removal 
of the excess of lead, gave a slight precipitate with potassium mer- 
curic iodide, and when heated with potassium hydroxide a strong 
ammoniacal odor was developed, thus indicating the probable pres- 
ence of soluble protein products. It readily reduced Fehling's solu- 
tion, and contained a large amount of sugar, which yielded <i-phenyl- 
glucosazone, melting and decomposing at 212°. It also contained 
some potassium salts, since the addition of an aqueous solution of 
picric acid to a portion of the liquid caused a gradual separation 
of crystals of potassium picrate. The main portion of the aqueous 
liquid was concentrated to the consistency of a syrup and kept for 
a considerable time, but nothing crystalline was deposited. 

The Resins (B). 

The resinous material which had been separated from the original 
alcoholic extract, as previously described, was a dark-colored, soft 
solid, and amounted to 694 grammes, thus representing about 8.7 
per cent, of the weight of the drug. It was digested with hot alco- 
hol, the liquid brought on to purified sawdust, and the thoroughly 
dried mixture then extracted successively in a large Soxhlet appa- 
ratus with various solvents. The amounts of the respective extracts, 
dried at 100°, were as follows: 

Petroleum (b. p. 35-50°) extracted 296.0 Gms. = 42.6 per cent. 
Ether " 226.0 " = 32.6 " " 

Chloroform " 38.2 " = 5.5 " " 

Ethyl acetate " 16.4 " = 2.4 " " 

Alcohol " 30.2 " = 4.4 " " 



Total 606.8 Gms. = 87.5 per cent. 

From these results it would appear that a portion of the resin 
had been rendered insoluble during the process of extraction. 

Petroleum Extract of the Resin. 

The petroleum extract of the resin consisted of a dark-colored, 
oily product, and amounted to 296 grammes. It was dissolved in 
a large volume of ether, and the ethereal liquid shaken with aqueous 



Am. Jour. Pharm. \ 
January, 1911. J 



Rhisome of Iris Versicolor. 



7 



ammonium carbonate, which, however, removed only traces of 
gummy matter. An attempt subsequently to extract the ethereal 
liquid with aqueous sodium hydroxide resulted in the formation of 
an emulsion, which did not separate after several days. The ether 
was therefore completely removed from the mixture, and the residue 
hydrolyzed by heating for an hour with an excess of alcoholic potas- 
sium hydroxide. After removing the greater portion of the alcohol, 
water was added, and the alkaline mixture shaken repeatedly with 
ether. These ethereal extracts were united, washed, dried, and the 
solvent removed, when a yellowish-brown, semi-solid mass was ob- 
tained. This amounted to 35 grammes, and represented the un- 
saponifiable portion of the petroleum extract of the resin. 

Isolation of a Phytosterol, C27H4gO, Myricyl Alcohol, CgiHg^O, and 
Heptacosane, Cot^^^. 

The above-described, brown, semi-solid mass was dissolved in 
a mixture of alcohol and ethyl acetate, and subjected to a process 
of fractional crystallization. The more soluble fraction ultimately 
yielded a crystalline substance, which separated from alcohol in 
colorless needles. This substance, when air-dried, melted at ISS"", 
but, when dried at 100°, it lost water of crystalHzation, and then 
melted at 148°. 

0.1714, when heated at 110°, lost 0.0076 HoO. HgO = 4.4 
0.1052, dried at 110°, gave 0.3236 COo and 0.1144 H2O. 

C = 83.9; H = 12.1 
CojH^gOjHsO requires H2O = 4.5 per cent. 
C27H4gO requires C = 83.9 ; H = 11.9 per cent. 

The above-described substance has thus been shown to agree in 
composition with a phytosterol of the formula Cs^H^gO, and it 
yielded the color reactions of that class of compounds. Its optical 
rotatory power was determined with the following result : 

0.1638 of anhydrous substance, made up to 25 c.c. with chloro- 
form, gave — 0° 28' in a 2 dcm. tube, whence [a]^ — 35-6°. 

The more sparingly soluble crystalline deposits obtained by the 
above-mentioned fractionation melted indefinitely over a consider- 
able range of temperature, namely from 63 to 77°, and apparently 
consisted of a mixture of a hydrocarbon and a fatty alcohol. They 
were therefore heated for an hour at 130° with an equal weight of 
phthalic anhydride in the presence of xylene. The product of the 
reaction was then dissolved in a mixture of ether and chloroform, 



8 



Rliizouie of Iris Versicolor. 



( Am. Jour. Pharm. 
I January, 1911. 



and the solution shaken with aqueous sodium carbonate, when the 
sodium salt of an acid phthalic ester was immediately deposited. 
The latter was collected, and washed with a mixture of ether and 
chloroform, and then hydrolyzed by heating with alcoholic sodium 
hydroxide. After removing the alcohol from the reaction product, 
water was added, and the fatty alcohol thus precipitated was col- 
lected and crystallized from ethyl acetate, when minute, colorless 
needles, melting at 84°, were obtained. This substance was analyzed 
with the following result : 

0.0913 gave 0.2742 COo and 0.1154 HoO. C = 8i.9; H = 14.1 
Co^H^j^O requires C = 82.3 ; H = 14.2 per cent. 

The compound was thus identified as myricyl alcohol. 

The ethyl acetate mother-liquors, remaining after the separation 
of the myricyl alcohol, yielded a small quantity of a crystalline sub- 
stance melting at 77-78°. The melting point of this compound, 
together with the method of its isolation, would indicate that it con- 
sisted of ceryl alcohol, but the amount of substance was too small 
for an analysis. 

The ether-chloroform solution which had been shaken with 
aqueous sodium carbonate to remove the myricyl acid phthalate, as 
above described, was evaporated, and the residue heated with alco- 
holic sodium hydroxide to remove the excess of phthalic anhydride. 
After evaporating the alcohol, and adding water to the residue, 
a small quantity of a solid was obtained, which was collected and 
recrystallized from ethyl acetate. It separated from this solvent in 
small, colorless leaflets, melting at 64-66°. 

0.0931 gave 0.2903 COo and 0.1230 HoO. € = 85.0; H = 14.7 
Co^H.^g requires C = 85.3 ; H = 14.7 per cent. 

It is evident from the analysis and the melting point determina- 
tion of this substance that it was heptacosane. 

Isolation of Ipuranol, CogHggOsCOH)^. 

The alkaline liquid obtained by the hydrolysis of the petroleum 
extract of the resin, having been extracted with ether to remove 
unsaponifiable material, as above described, was next acidified with 
dilute sulphuric acid, when the fatty acids were precipitated as a 
dark-colored oil. The mixture was then shaken with ether, which 
dissolved the fatty acids, leaving, however, a small quantity (0.7 
gramme) of a green solid undissolved. The latter was collected, 
washed with hot alcohol, and recrystallized from pyridine containing 



Am. Jour. Pharm. 1 
January, 1911. j" 



Rhizome of Iris Vei'sicolor. 



9 



a little alcohol. It separated from this solvent in stellar aggregates 
of small, colorless needles, which decomposed at 285-295°. 

0.0648 gave 0.1718 CO2 and 0.0600 HoO. C = 72.3 ; H = 10.3 
C23H40O4 requires C = 72.6 ; H = 10.5 per cent. 

This compound, when dissolved in chloroform with a little acetic 
anhydride, and a drop of concentrated sulphuric acid subsequently 
added, gave a transient pink coloration, rapidly changing to blue 
and green. It yielded an acetyl derivative, which crystaUized in 
colorless leaflets melting at 162-163°, and when this was mixed 
with a known specimen of diacetylipuranol the melting point re- 
mained unaltered. 

The above-described compound was thus definitely identified as 
ipuranol (compare this Journal, 1908, 80, pp. 264, 576; Journ. Cheni. 
Soc./ igo8, 93, p. 907; 1909, 95» p. 249; 1910, 97, pp. 7, 1 102; Pharm. 
Journ., 1910, 84, p. 327). 

Examination of the Fatty Acids. 

The ethereal solution of fatty acids, from which the ipuranol 
had been separated, was washed with water, dried with anhydrous 
sodium sulphate, and the solvent removed. The residue, amounting 
to about 210 grammes, was dissolved in absolute ethyl alcohol, and 
esterified by passing a current of dry hydrochloric acid gas into the 
boiling solution. The excess of alcohol was then evaporated, the 
residual oil taken up by ether, and the ethereal solution washed, 
first with aqueous sodium hydroxide, which extracted a quantity 
of resinous substance, and then with water until free from alkali. 
After drying the solution, and removing the ether, the residual 
ethyl ester was fractionally distilled under diminished pressure, 
when 5 fractions were ultimately obtained, possessing the following 
constants : 



Fraction B. p. Saponification Value Iodine Value 

1. I40-i55%omn,. 249 2.5 

2. i55-i75V2o„™ 242 4.7 
3- i75-i95%omm. 224 15.3 

4. 195-225 %Omm. 51.7 

5. above 225%o^^ 



Fraction i. — This fraction, amounting to 12 grammes, distilled 
under atmospheric pressure at 260-270°. It possessed a fruity 
odor, and, from a consideration of its boiling point and saponification 



lO 



Rhizoluc of Iris V ersicolor. 



(Am. Jour. Phann. 
\ January, 1911. 



value, appeared to consist chiefly of ethyl laurate(l). p. 269° ; saponifi- 
cation value 246) . In order to confirm the presence of lauric acid, 
the entire fraction was hydrolyzed with alcoholic potassium hydrox- 
ide, and the mixture then acidified and distilled in a current of 
steam. A quantity of volatile fatty acid was thus obtained, which 
melted at 40°, and was further identified as lauric acid by means of 
its neutralization value. 

0.3150 required for neutralization 15.7 c.c. Ba(OH)2. 

Neutralization value = 280. 
C12H04O0 requires Neutralization value = 280. 

Fractions 2 and 3. — These fractions, which were small in amount, 
were united and hydrolyzed with alcoholic potassium hydroxide, in 
order to obtain the free fatty acids. The latter were then dissolved 
in hot alcohol, and separated into four dififerent fractions by the 
successive ad^dition of small quantities of concentrated aqueous 
barium acetate. These fractions of barium salt yielded acids which 
melted at 33-35°, 33-35°. 35-36°, and 39°, and whose neutralization 
values were 260, 261, 268, and 275 respectively. It was evident 
from these results that fractions 2 and 3 consisted of a mixture of 
lauric acid (neutralization value = 280) and the acids of higher 
carbon content contained in the succeeding fraction. 

Fraction 4. — This fraction contained the greater portion of the 
total fatty acids, and amounted to 120 grammes. Its iodine value 
(51.7) indicated the presence of a considerable quantity of unsat- 
urated acid. For its further examination the acids were regener- 
ated by hydrolysis, and then fractionally precipitated in hot alcoholic 
solution with small portions of concentrated aqueous barium acetate. 
In this manner the saturated acids were precipitated in the first 4 
fractions, while the final fraction, which was oily, contained the 
unsaturated acids, and was therefore put aside for subsequent 
examination, as described below. The barium salts of the saturated 
acids thus obtained were treated separately with dilute hydrochloric 
acid, and the liberated fatty acids recrystallized from alcohol. The 
several fractions were then found to melt at 54-56°, 54-56°, 54-55°. 
and 53-55° respectively, while the corresponding neutralization 
values were 209, 212.5, 216, and 217. It was evident from these 
results that the saturated acids contained in fraction 4 consisted of a 
mixture of stearic and palmitic acids, whose neutralization values 
are 198 and 219 respectively. 



Am. Jour. Pharm. \ 
January, 1911. j 



Rhizome of Iris Versicolor. 



II 



The unsaturated acids, which were regenerated from the above- 
mentioned oily barium salt, still contained small quantities of satur- 
ated acids. The mixture was therefore converted into its lead salt, 
and the latter treated with cold ether. The portion insoluble in ether 
was found upon examination to consist of the lead salts of lauric 
and palmitic acids. The portion soluble in ether, when treated with 
dilute hydrochloric acid, yielded the unsaturated acids as a pale 
yellow oil, which possessed the following constants : neutralization 
value = 208 ; iodine value = 1 1 1. 

In order to ascertain the constituents of the unsaturated acids, 
12 grammes of the mixture were oxidized with dilute alkaline per- 
manganate, as described by Lewkowitsch (Chemical Technology and 
Analysis of Oils, Fats, and Waxes, 1904, vol. i, p. 360), when the 
chief oxidation product was dihydroxystearic acid, melting at 128°. 
0.3412 required for neutralization 10.95 c.c. KOH. 

Neutralization value = 180. 
CtsH.,,.0^ requires Neutralization value = 178. 
A small quantity of tetrahydroxystearic acid (sativic acid), melt- 
ing at 156°, was also isolated. 

0.3164 required for neutralization 9.1 c.c. KOH. 

Neutralization value = 164. 
CisHggOf; requires Neutralization value = 164. 
No linusic or /^clinusic acid was present in the product of oxida- 
tion, and it may therefore be concluded that the unsaturated acids 
consisted of a mixture of oleic and linolic acids, the former pre- 
dominating. 

Isolation of Cerotic Acid, CorH-^oOo. 

Fraction 5. — The final fraction obtained by the distillation of the 
esters of the total fatty acids solidified in the receiver as a colorless 
solid. It was recrystallized several times from alcohol, when it 
separated in glistening leaflets, melting at 55-56°. This ester was 
then hydrolyzed, and the liberated fatty acid recrystallized from 
ethyl acetate. It was deposited from this solvent in colorless leaflets, 
melting at 78°, and was identified as cerotic acid. 
o.Tiio gave 0.3185 CO. and 0.1295 H.O. C = 78.3 ; H = 13.0 
0.1822 required for neutralization 4.75 c.c. KOH. 

Neutralization value = 146. 
CocHr.^.O^ requires C = 78.8; H = 13. i per cent. Neutralization 
value = 142. 



12 



Rliizome of Iris Versicolor. 



f Am. Jour. Pharm. 
I January, 1911. 



Ethereal Extract of the Resin. 

This was a hard, black, brittle mass, and amounted to 226 
grammes. It was digested with a large volume of ether, when a 
small portion of the resin (2 grammes) was found to be sparingly 
soluble in that solvent. The ethereal liquid was therefore filtered, 
and the undissolved portion separately examined. It was found to 
consist of ipuranol, C^gH^^O^, which was identified by means of its 
diacetyl derivative, melting at 161-162°. This substance had 
already been isolated from the petroleum extract of the resin. 

The ethereal liquid, from which the ipuranol had been removed 
by filtration, was then successively extracted with aqueous solutions 
of ammonium carbonate, sodium carbonate, and sodium hydroxide 
respectively. The ammonium carbonate and sodium carbonate solu- 
tions extracted only small quantities of amorphous, brown resins, 
from which no definite compound was isolated. The aqueous 
sodium hydroxide, on the other hand, extracted practically the whole 
of the resin as a thick, black liquid, a small quantity of the alkali 
being sufficient to extract a comparatively large amount of the resin, 
thus indicating that the latter possesses a very high molecular weight. 
On acidifying the alkaline extract, a brown, amorphous solid was 
precipitated, which was readily soluble in ether and alcohol. All 
attempts to isolate a crystalline compound from it were, however, 
unsuccessful. In order to ascertain whether the resin was glucosidic 
in character, a portion of it was heated for some time in alcoholic 
solution with dilute aqueous sulphuric acid. On removing the alco- 
hol in a current of steam a quantity of resinous matter separated, 
which was collected and examined, but it yielded nothing crystalline. 
The aqueous liquid, after being freed from sulphuric acid by means 
of baryta was concentrated and tested for the presence of sugar, 
but with a negative result. The portion of resin extracted by ether 
is therefore non-glucosidic. 

The ethereal liquid which had been shaken with alkalies, as above 
described, was washed, dried, and the solvent removed, when a small 
quantity of a thick oil was obtained. This was found to be similar 
in character to the petroleum extract of the resin, which had already 
been exhaustively examined. 

Chloroform, Ethyl Acetate, and Alcohol Extracts of the Resin. 

These were all black, brittle resins, and were small in amount. 
They were each carefully examined, but nothing of a crystalline 



^jan'^aiT im""*} Rhisome of Iris Versicolor. 13 

character could be isolated from them. Both the ethyl acetate and 
alcohol extracts of the resin were specially tested for the presence 
of a glucoside, but with a negative result. 

SUMMARY AND PHYSIOLOGICAL TESTS. 

The results of the present investigation of Blue Flag Root " 
(the rhizome and roots of Iris versicolor, Linne), together with 
some physiological tests and the deductions therefrom, may be sum- 
marized as follows : 

The material employed was the commercial drug, the genuineness 
of which was established, and it appeared to be of good quality. A 
preliminary test with a small portion of the material showed the 
absence of an alkaloid, and in the course of the investigation no evi- 
dence was obtained of the presence of a glucoside. 

An alcoholic extract of the ground material, when distilled with 
steam, yielded a small amount of an essential oil, which possessed a 
yellow color, a strong, rather unpleasant odor, and had a density of 

0.9410 at 20°/20°. 

The portion of the extract which was soluble in water contained 
a little i^cphthalic acid, C6H^(C02H)2, which has not previously 
been observed to occur in nature, and apparently a trace of salicylic 
acid, together with tannin, and a sugar which yielded (i-phenylgluco- 
sazone (m. p. 212°). 

The portion of the extract which was insoluble in water con- 
sisted chiefly of a dark colored, soft resin, amounting to about 8.7 
per cent, of the weight of the drug. From this resin the following 
definite products were isolated : A phytosterol, Co7H4gO,H20 (m. p. 
when anhydrous, 148°; [a] ^ — 35-6°); myricyl alcohol, C3iHg40 , 
heptacosane, CsjHgg ; ipuranol, Co3H3gOo(OH)o ; and a mixture of 
fatty acids, consisting of lauric, palmitic, stearic, cerotic, oleic, and 
linolic acids. 

As no definite substance had been isolated in the course of this 
investigation to which the reputed properties of Blue Flag Root " 
could be attributed, the following crude products therefrom were 
kindly tested for us by Dr. H. H. Dale, Director of the Wellcome 
Physiological Research Laboratories, to whom we desire here to 
express our thanks : 

I. The total alcoholic extract. 

TI. The total resinous material, 

TIL The portion of the alcoholic extract which was soluble in 
water. 



14 



Note on Lactic Acid. 



f Am. Jour. Pharm. 
( January, 1911. 



IV. An aqueous extract of the drug, prepared without heat. 

Each of these preparations was given to a dog by the mouth, 
Nos. I and II in amounts of i gramme, and III and IV in consider- 
able quantity. No vomiting or modification of the faeces was pro- 
duced, nor could any other sign of activity be detected. 

Although the potency of " Blue Flag Root," in the fresh state, 
is evidently well estabHshed, it has also been recorded that its medic- 
inal activity is impaired by age. From the results of the above 
experiments, it would appear that it is possible for the drug com- 
pletely to lose its physiological activity. 



A NOTE ON THE ASSAY OF LACTIC ACID. 
By Elias Elvove. 

Hygienic Laboratory, U. S. Public Health and Marine-Hospital Service. 

Washington, D. C. 

It has been pointed out by Murray ^ that the assay requirement 
of the U. S. Pharmacopoeia in the case of lactic acid (75 per cent.) 
is out of harmony with its specific gravity requirement since a mix- 
ture of 75 per cent, lactic acid and 25 per cent, water has a specific 
gravity of about 1.175 at 25° C, whereas the U.S. P. specific gravity 
requirement (" about 1.206 at 25° C") would correspond to a mix- 
ture of 85 to 88 per cent, lactic acid and 12 to 15 per cent, water. 
It occurred to the writer that this discrepancy might possibly be 
due to a weak point in the assay method which may cause the acid 
to appear weaker than it actually is. This further suggested the 
desirability of avoiding, if possible, the titration of the acid at a 
boiling temperature as called for by the present U.S. P., since the 
titration at a boiling temperature instead of at ordinary temperature 
involves not only comparative inconvenience but is also more liable 
to yield different results in the hands of different operators. 

A consideration of the circumstances of this case appears to show 
that it is possible to avoid carrying out the titration at a boiling tem- 
perature. For it is quite probable that the object of the boiling 
is to reconvert into acid any lactone anhydride which may be present. 
And since it is known ^ that lactones in general do not take up 
water by mere boiling or are only partially converted into acid by 
such treatment, but are converted into salts of the corresponding 

^Merck's Report, N. Y., 16, 248 (1907). 

"Watts' Dictionary of Chemistry, vol. iii, p. 114 (1901). 



Am. Jour. Pharm. ) 
January, 1911. j 



Note on Lactic Acid. 



15 



acids by boiling with aqueous solutions of alkalies, it would seem 
that a much better plan for recovering the acid value of such anhy- 
drides is to boil with a measured excess of a standard solution of 
alkah and determine the amount of alkali which remains uncom- 
bined by titration (at ordinary temperature) with a standard solu- 
tion of acid. On looking into the matter, it was found that in the 
French Pharmacopoeia (1908) such a plan has actually been adopted, 
the procedure consisting essentially in adding a measured excess of 
alkali, boihng for fifteen minutes, cooling, and then titrating the 
residual alkali. It was thought desirable, therefore, to obtain some 
comparative data concerning both this residual titration process and 
that in which the titration is carried out at a boihng temperature. 

On titrating a dilute aqueous solution of lactic acid at a boiling 
temperature it was found that the result thus obtained may vary 
within comparatively wide limits, depending on what is taken as 
indicating the end-reaction, whether the coloring of the solution by 
the phenolphthalein indicator and its remaining on mixing the solu- 
tion (first indication of neutrality), or whether the boiHng is to be 
continued for some time after that point has been reached, and the 
length of time the boiling is continued after the first indication of 
neutrality. In the following work, therefore, two procedures were 
used in carrying out the titration at a boiling temperature. In one 
of these (designated as No. 2 in the Tables), the solution was first 
titrated to neutrality at ordinary temperature and the standard 
alkali then added in small portions (three drops) at a time and 
boiled after each such addition of the alkali until a decided pink 
color remained after the boiling had continued for one minute longer. 
The other procedure in which the titration was completed at a boiling 
temperature (designated as No. 3 in the Tables) was carried out in 
exactly the same way, but the titration was not considered ended 
until a decided pink color had remained after the boiling had been 
continued for ten minutes longer. Likewise, in the case of the resid- 
ual titration after treatment with an excess of alkali, two procedures 
were used. In one of these (designated as No. 4 in the Tables), 
the stated amounts of the acid and alkali were well mixed and 
allowed to stand thirty minutes at ordinary temperature before 
titrating the excess alkali. In the other (designated as No. 5 in 
the Tables), the mixture was boiled for fifteen minutes, cooled, and 
the excess alkali then titrated with the standard acid. And in the 
latter case, in order to avoid any possibility of the alkali becoming 



i6 



Note on Lactic Acid. 



( Am. Jour. Bharm. 
\ January, 1911. 



contaminated with the carbon dioxide which is given off by the 
flame of the burner, the boihng was effected in Erlenmeyer flasks 
which were fitted with india-rubber sHt valves (Bunsen's valve). 
Eight samples of lactic acid were examined, the solution of each 
being also titrated directly at ordinary temperature (designated as 
procedure No. i in the Tables). Seven of these samples were 
obtained from American firms, while one was obtained from a Ger- 
man firm (Kahlbaum). The results obtained are given in the 
following tables : 

TABLE I. 



Shozving Lactic Acid Strength of Various Commercial Samples of 
Lactic Acid as Determined by Various Procedures. 







Amount of 


N/io NaOH 




Lactic acid 


No. of 


No. of 


lactic acid so- 


added before 


N/io NaOH 


strength of 


sample. 


procedure 


lution taken. 3 


titration. 


required. 


sample. 






(c.c.) 


(c.c.) 


(c c.) 






J 


20 





TO nC 


72 \A 








r\ 
\J 


T rv~» 






3 




r\ 
U 




o5o9 




4 








87 67 




5 


20 


40 


23.15 


87.67 


2 


I 


20 





18.30 


71.95 


2 


2 


20 





21.10 


82.95 


2 


3 


20 





2T.9O 


86.10 


2 


4 


20 


40 


22.45 


88.26 


2 


5 


20 


40 


22.55 


88.65 


3 


I 


20 





18.05 


71.86 


3 


2 


20 





21.00 


83.63 


3 


3 


20 





21.60 


85.99 


3 


4 


20 


40 


22.40 


89.18 


3 


5 


20 


40 


22.40 


89.18 


4 


I 


20 





18.40 


71.72 


4 


2 


20 





21.25 


82.83 


4 


3 


20 





22.00 


85.75 


4 


4 


20 


40 


22.60 


•88.10 


4 


5 


20 


40 


22.70 


88.48 



*The solutions of lactic acid used contained the following amounts in 
grammes of the respective samples of lactic acid in 1000 c.c. of the solution : 
No. I, 11.8825; No. 2, 11.4463; No. 3, IL3034; No. 4, 11.5446; No. 5, 11.7030; 
No. 6, IL6975; No. 7, IL5736; No. 8, 11.5892. 



Am. Jour. Pharm. ) 
January, 1911. j 



Note on Lactic Acid. 



17 



TABLE I. — Continued. 



No. of 
sample. 


No. of 
procedure 


Amount of 
lactic acid so- 
lution taken. 3 
(c.c.) 


N/io NaOH 
added before 
titration, 
(c.c.) 


N/io NaOH 
required, 
(c.c.) 


Lactic acid 
strength of 
sample. 


5 


I 


20 





18.70 


71.90 


5 


2 


20 





21.70 


83-44 


5 


3 


20 





22.55 


86.71 


5 


4 


20 


40 


23-15 


89.01 


c 
5 


5 




40 


23.20 


09.21 


6 


I 


20 





18.65 


71-75 


6 


2 


20 





21.60 


83.09 


6 


3 


20 





22.60 


86.94 


6 


4 


20 


40 


23.20 


89.25 





5 


20 


40 


23-25 


«9.44 


7 


I 


20 





18.70 


72.71 


7 


2 


20 





21.50 


83-59 


7 


3 


20 





22.25 


86.51 


7 


4 


20 


40 


23.10 


89.82 


7 


5 




40 


23.10 


09.02 


8 


I 


20 





18.35 


71-25 


8 


2 


20 





22.45 


87.17 


8 


3 


20 





23-75 


92.22 


8 


4 


20 


40 


24.30 


94-35 


8 


3 


20 


40 


24-35 


. 94-55 






TABLE II. 






Showing the Results Obtained 


on Titrating 


Lactic Acid with Nor- 




mal Alkali by Various Procedures. 




No. of 
experiment 


No. of 

procedure^ 


Amount of 
sample taken. 
(Gm.) 


N/i NaOH 
added before 
titration. 5 
(c.c.) 


N/i NaOH 
required, 
(cc.) 


Lactic acid 
strength of 
sample. 
(Per cent.) 


I 


I 


2.4280 





19.50 


72.28 


2 


2 


2.4280 





23.20 


85.99 


3 


3 


2.4280 





23-35 


86.55 


4 


4 


2.4143 


50 


23-50 


87.60 


5 


5 


2.3649 


50 


23.12 


87:99 


6 


6 


2.3899 


50 


23.27 


87.63 



* Procedure No. 6 differed from No. 4 only in that the alkaline mixture 
was allowed to stand fifteen minutes instead of thirty, before titrating the 
excess alkali. 

° Where no alkali was added before the titration an equal volume of 
water was added instead. 



i8 



Note on Lactic Acid. 



( Am. Jour. Pharm. 
\ January, IBll. 



It appears from the results given in the above Tables that the 
titration of lactic acid at a boiling temperature is not only avoidable, 
but may even yield varying and considerably lower results than by 
the residual titration process. Further, the residual titration process 
is applicable even to dilute (about tenth-normal) aqueous solutions 
of the lactic acid when the amount of alkali added is about twice 
the amount necessary to neutralize all the lactic acid, and that prac- 
ticably as close results may be obtained even if the mixture is not 
boiled but simply allowed to stand at ordinary temperature for half 
an hour before titrating the excess alkali ; all of the samples of lactic 
acid examined showing a greater acid strength even by the latter pro- 
cedure than when titrating at a boiling temperature and taking the 
end-reaction as that point when the color of the indicator will not 
completely disappear even by continuing the boiling for ten minutes 
longer. These results also show that the residual titration process 
indicates an acidity which is quite in harmony with the U.S. P. 
specific gravity requirement; while the fact that the present U.S. P. 
acidity requirement of 75 per cent, is only comparatively little 
above that which most of the samples examined showed (about 
72 per cent.) on direct titration at ordinary temperature (procedure 
No. i) and considerably below that shown by procedures Nos. 2 
and 3 (about 83 to 86 per cent.), would indicate that the first 
appearance of neutrality was taken as the end-reaction by the author 
of the present U.S. P. method. It is also seen that none of the 
eight samples examined showed an acid strength of less than 87 
per cent, when assayed by the residual titration process. A require- 
ment of not less than 85 per cent, instead of the present requirement 
of not less than 75 per cent, would, therefore, come nearer the 
actual strength of the lactic acid on the market and would also 
fairly harmonize this requirement with the specific gravity require- 
ment. Finally, it may be mentioned in this connection that, as shown 
by Utz,^ lactic acid is volatile with water vapor and hence for this 
reason also it would seem best to avoid boiling its aqueous solution 
when it is desired to estimate its quantity. Likewise, from the point 
of view of the time required for the assay, the residual titration 
process is certainly not at a disadvantage in the comparison. For 
when titrating at a boiling temperature, from about twenty minutes 
(procedure No. 2) to about forty minutes (procedure No. 3) was 

''Chem. Zeit, 29, 363-364 (iQOS). 



« 



Am. Jour. Pharm. i 
January, 1911. j 



Note on Sulphur Dioxide. 



19 



required for each titration ; whereas in the residual titration process 
not more than thirty minutes need be consumed for the correspond- 
ing part of the assay, and even during this time the attention of the 
operator is not required as closely and repeatedly for each titration 
as when the titration is carried out at a boiling temperature, and 
no attention at all is required from the operator during this period 
when the mixture is simply allowed to stand at ordinary tempera- 
ture. It would seem, therefore, that the residual titration process 
has many advantages over the method in which the titration is car- 
ried out at a boiling temperature, which should justify its adoption 
in the next revision of the U.S. P. And since practically as close 
results are obtained by simply mixing well the acid with about twice 
the amount of alkali required and allowing the mixture to stand from 
fifteen to thirty minutes before titrating the excess alkali, as when 
the alkaline mixture is boiled for fifteen minutes, it would seem that 
'the boiling might be entirely omitted, and the assay method for 
lactic acid modified to read somewhat as follows : 

To about two grammes of the sample of lactic acid, accurately 
weighed, add 50 c.c. of normal NaOH, mix well, and let stand for 
half an hour. Then titrate the excess alkali by means of normal 
sulphuric acid, using phenolphthalein as indicator. The number 
of cubic centimetres of the alkali found to be required, multiplied 
by the lactic acid equivalent of i c.c. (0.09 Gni.), and this product 
divided by one-hundredth of the weight of the sample taken for the 
assay, will express in percentage the lactic acid strength of the 
sample. 



A NOTE ON THE USE OF SULPHUR DIOXIDE IN CHECK 
ING THE EQUIVALENCIES OF THE VOLUMETRIC 
SOLUTIONS OF IODINE, ALKALI, AND SILVER. 

By Eli as Elvove. 

Hygienic Laboratory, U. S. Public Health and Marine-Hospital Service, 

Washington, D. C. 

In connection with some tests which are being carried out at 
the Hygienic Laboratoi-y on the efficiency of a sulphur burning 
stove, designed by Dr. Norman Roberts and Mr. F. A. McDermott 
of this laboratory, the writer has had occasion to estimate the 
relative amounts of SO^ and SO;j formed in these combustions, by 



20 



Note on Sulphur Dioxide. 



( Am. Jour. Pharm. 
( January, 1911. 



the method of Kastle and McHargue.^ This method depends on 
the reaction expressed by the equation 

I2 + SO, + 2H,0 = 2HI + ; 
from which it is seen that for every equivalent of iodine two equiva- 
lents of acid result. Hence by determining both the amount of 
iodine used up in the reaction and also the total acidity after the 
reaction, we can estimate both the SO, and SO3, since the found 
excess acidity over that required by the above equation would be 
a measure of the SO3 originally present. In the work of Kastle and 
McHargue, the exact strength of the thiosulphate solution was 
determined by means of Kahlbaum's resublimed iodine immediately 
before each experiment and the exact strength of the iodine solution 
determined by means of the thiosulphate. The exact strength of the 
sodium hydroxide was frequently determined by means of weighed 
amounts of pure oxalic acid. 

In this connection, it occurred to the writer that the above reac- 
tion between SO, and iodine might be used with advantage in 
checking the equivalencies of the standard iodine and hydroxide 
solutions ; and if instead of using an approximate amount of 
potassium iodide ("about 18 Gm." ^ per litre) in the preparation 
of the iodine solution, an accurately weighed amount of KI (say 
16.602 Gm.^ per litre) were used, the purity of which has been 
accurately ascertained by means of the standard silver solution, the 
values of the iodine and hydroxide solutions could be directly com- 
pared, in the same solution, with the standard silver solution; 
which, as pointed out by the writer,^ might be used with advantage 
in the standardization of all of the volumetric solutions ordinarily 
employed. And, since the value of the permanganate solution can 
be ascertained by titrating with thiosulphate (the strength of which 
is measured by the iodine solution) the amount of iodine which a 
definite amount of the KMnO^ can liberate from a solution of KI 
acidified with sulphuric acid, if we prove the accuracy of our iodine 
solution in terms of the silver solution we can thus also check the 
accuracy of the value assigned to the permanganate solution. In 

Amer. Chem. Jour., 38, 465-475 (1907); and Chem. News, 96, 236-238 
(1907). 

" Sutton : Volumetric Analysis, 9th ed., p. 133. 

^ This amount of KI per litre would yield a solution exactly tenth-normal 
(using the 1910 international atomic weights). 
^ Amer. Jour. Pharm., 82, 203-211 (1910). 



Am. Jour. Pharm. \ 
January, 1911. j 



Note on Sulphur Dioxide. 



21 



other words the reaction between sulphur dioxide and iodine might 
be made, so to speak, the connecting Hnk whereby the typical repre- 
sentatives of the four different classes of volumetric solutions, 
namely, the permanganate, iodine, alkali, and silver solutions, are 
connected together and their relative values established and referred 
back to the silver solution which was used in their first standard- 
ization. 

The standardization and checking of the volumetric solutions as 
thus outlined seems especially advantageous in the case referred 
to above (the volumetric estimation of SOo and SO3 when occur- 
ring together), for not only would we be able to refer all the results 
to one standard instead of two different standards (e.g., iodine and 
oxalic acid), but we could also base the entire work on a standard 
which is more readily kept unaltered and is more convenient than is 
the case with solid iodine. Thus, for example, in the estimation of 
the SOo and SO... by the method of Kastle and McHargue, we might 
base the entire work on the value of our standard sulphuric acid 
solution. By means of the latter, the value of the NaOH solution 
could be readily ascertained ; and by just decolorizing a definite 
amount of the iodine solution with a dilute, freshly prepared solution 
of sulphur dioxide (the strength of which need not be known) and 
determining the total acidity by means of the NaOH solution, we 
would obtain a check on the correctness of the assigned relative 
values of the iodine and hydroxide solutions ; and since the result- 
ing iodide could now be determined by means of the standard 
silver solution, we would thus obtain a check on the value of the 
iodine solution by direct reference to the standard silver solution. 
In this way we would not only avoid the weighing and handling of 
the solid iodine every time we want tO' check our solutions, but 
would also base the entire work on a single standard ; and having 
found that when working with the solution of pure sulphur dioxide 
the results obtained are in close agreement with the theory, we could 
feel more certain when working in this way than when employing 
the double standard, that the subsequent results with the mixture 
of SO. and SO.,, however slight the variation may be from the 
results as obtained with the pure SOo, are not due to any error 
in the standardization of our solutions, but solely to the presence of 
a small amount of SO... 

The following data will illustrate the plan for standardizing 
all the ordinary volumetric solutions by means of pure mietallic silver 



22 



Note on Sulphur Dioxide. 



3 Am. Jour. Phann. 
1 January, 1911. 



as the ultimate standard and the suhsequent checking of the equiva- 
lencies thus found, by means of the reaction between sulphur dioxide 
and iodine. All the solutions were prepared in the ordinary way 
except the iodine solution, in the case of which an accurately weighed 
amount of pure KI, 16.602 Gm. per litre, was used instead of about 
18 Gm." which is ordinarily used. Of this KI, 0.5442 Gm. was 
found equivalent to 32.7 c.c. of the n/io AgNO.^ solution. This 
would make the iodine solution 99.85 per cent, tenth-normal with 
reference to its KI content, which value was used in the subsequent 
calculations. The water used was free from oxygen and carbon 
dioxide. When a fairly rapid current of SO2 is available, the 
time required for obtaining about 50 c.c. of the sulphur dioxide solu- 
tion, of a strength suitable for the present purpose, need not exceed 
fifteen seconds ; hence no special care was taken to entirely avoid 
contact of the liquid with the atmosphere, but the SOo solution thus 
obtained was quickly transferred to a burette and used immediately 
for decolorizing the iodine solution. The following results were 
obtained by working according to the plan above outlined. 

1. Used 0.4287 Gm. of the pure metallic silver (equivalent to 
39.74 c.c. n/io AgNO.,) and found it to require 39.62 c.c. of the 
n/io NH.CNS. Therefore, the normality of the NH.CNS solu- 
tion, expressed in percentage of an exact n/io solution, is 100.30. 

2. Found that 50 c.c. of the n/io AgNO.. are equivalent to 49.9 
c.c. of the above n/io NH^CNS. Therefore, the normality of the 
AgNOo solution, expressed as above, is 100.10. 

3. Found that 45 c.c. of the n/io HCl are equivalent to 45.25 
c.c. of the above n/io AgNOo. Therefore, the normality of the 
HCl solution, expressed as above, is 100.65. 

4. Found that 45 c.c. of the above n/io HCl are equivalent to 
45.05 c.c. of the n/io NaOH. Therefore, the normahty of the 
NaOH solution, expressed as above is 100.54. 

5. Found that 45 c.c of the n/io oxalic acid are equivalent to 
44.7 c.c. of the above n/io NaOH. Therefore, the normality of 
the oxalic solution, expressed as above, is 99.86. 

6. Found that 45 c.c. of the above n/io oxalic acid are equivalent 
to 45.15 c.c. of the n/io KMn04. Therefore, the normality of the 
KMn04 solution, expressed as above, is 99.53. 

7. Found that 45 c.c. of the above n/io KMnO^ are equivalent 
to 45.45 c.c. of the n/io NaoSoO.. Therefore, the normahty of 
the thiosulphate solution, expressed as above, is 98.55. 



Am. Jour. Pharm. | 
January, 1911. j 



Note on Sulphur Dioxide. 



23 



8. Found that 50 c.c. of the above n/io NaoSoOg are equivalent 
to 49.5 c.c. of the n/io iodine. Therefore, the normaHty of the 
iodine solution, expressed as above, is 99.55. 

Control. — Used 25 c.c. of the above n/io iodine. This was just 
decolorized by means of a dilute, freshly prepared aqueous solution 
of SO2. On titrating- the total acidity with the above N/^^oNaOH. it 
was found to require 49.7 c.c. The solution was then acidified with 
5 c.c. of 10 per cent, nitric acid, 55 c.c. of the above n/io AgNO^ 
added, and the excess silver in the filtrate determined by means 
of the above n/io NH^CNS. In this way, it was found that the 
total iodide in the solution was equivalent to 49.85 c.c. of the above 
n/io AgNOs (or 49-9 c.c. of an exact n/io AgNOg). Subtracting 
from this 24.96 c.c. (the calculated value, in terms of n/io AgNO., 
of the added KI in the 25 c.c. of the iodine solution), it would 
make the 25 c.c. of iodine equivalent to 24.94 c.c. of an exact 
n/io AgNOg. 

Expressed in percentage of an exact n/io solution, we would 
have as the value of the iodine solution by the SO2 control, 99.76. 

Corresponding value as found through the use of the above- 
mentioned intermediary solutions, 99.55. 

On the basis of the iodine solution being 99.76 per cent, tenth- 
normal, it should have required 49.88 c.c. of an exact n/io NaOH. 
Now, since only 49.7 c.c. of the above n/io NaOH was required, it 
would show that the latter is a little stronger than tenth-normal. 

Expressed in percentage of an exact n/io solution, we would 
have as the value of the NaOH solution by the SOo control, 100.36. 

Corresponding value as found through the use of the above- 
mentioned intermediary solutions, 100.54. 

These results may be considered as showing a fair agreement 
between the first standardization by the silver solution, through the 
use of the above-mentioned intermediary solutions, and the SO^ con- 
trol, especially when it is remembered that an error of one drop in 
any of the measurements or titrations would correspond to a differ- 
ence of about 0.1 to 0.2 per cent. It would seem, therefore, that the 
reaction between sulphur dioxide and iodine might be used as a 
convenient check on the found equivalencies of the iodine and hy- 
droxide solutions in terms of the substance chosen as the ultimate 
standard — pure metallic silver. • 



24 



Tenth International Congress. 



{ Am. Jour. Phann. 
( January, Ittll. 



REPORT OF THE PROCEEDINGS OF THE TENTH INTER- 
NATIONAL CONGRESS OF PHARMACY, BRUS- 
SELS, SEPTEMBER i-6, 1910.* 

By Reid Hunt, 

Professor of Pharmacology, Hygienic Laboratory, United States Public 
Health and Marine-Hospital Service. 

The opening session was held in the Palais des Academies Sep- 
tember 1. More than 600 delegates, about one-half of whom came 
from countries other than Belgium, were present. Sixteen foreign 
governments had formally accepted the invitation to participate in 
the congress, and 20 were represented by official delegates. Dele- 
gates were present from the following American Republics : Argen- 
tina, Chile, Venezuela, Guatemala, San Salvador, Haiti, and the 
United States. 

The work of the congress was outlined at the opening meeting, 
at which the governor of Brabant, representing the minister of the 
interior ; the president and secretary of the congress ; and several of 
the foreign delegates, made addresses. The speakers emphasized, 
as the two subjects of greatest international interest: (i) The fur- 
ther unification of the pharmacopoeias, with special reference to the 
adoption of uniform methods of assay of important drugs ; and 
(2) the control of the sale of specialties (proprietary medicines), 
from the stand-point of public health as well as that of the material 
interests of the pharmacists. The governor of Brabant, M. Beco, 
formerly of the ministerial department having control of public 
health, hygiene, and pharmacy, urged the congress to add to its 
programme the subject of public hygiene, stating that he did not 
believe that pharmacists are as well qualified to deal with the prob- 
lems of this subject as is desirable, and pointing out the possibilities 
of pharmacists securing for themselves a more privileged position 
if they will extend their activities beyond the narrower commercial 
pursuits. 

The service of the Belgian Government in connection with the 
conference of 1902, which resulted in the securing of a greater de- 
gree of uniformity in the formulas of heroic medicines in the various 
pharmacopceias, was the subject of much favorable comment on the 
part of several of the foreign delegates. 

* Public Health Reports, volume xxv, No. 40, 1910, pp. 1406-1408. 



A.m. Jour. Pharm. ) 
January, 1911. j 



Tenth International Congress. 



25 



On the succeeding- days the congress met in two sections — 
scientific and professional. At each of these certain general ques- 
tions, announced in advance, were discussed. A considerable num- 
ber of communications, dealing for the most part with subjects of 
general scientific importance and all of international interest, were 
also presented. As a result of these discussions a number of reso- 
lutions were drawn up and voted upon, first by the sections and 
secondly by the entire congress at its concluding session September 6. 

The first of the resolutions, presented by the scientific section, 
related to the unification of the methods for the assay of crude 
drugs and of galenical preparations, and for the determination of 
physical constants. The great importance of this subject, from the 
stand-point not only of medicine but also from that of international 
commerce, was emphasized. The congress requested the Belgian 
government to call an international conference for the unifying of 
the methods of analysis of the heroic medicaments ; it also expressed 
the hope that, in the n-fktter of alkaloidal assays, the commission 
would adopt, as far as possible, gravimetric methods. These con- 
clusions and resolutions were based largely upon a paper by Doctor 
Schamelhout, who treated the subject from the stand-point of a 
practical pharmacist. 

The second resolution related to the international unification 
of the reagents used in pharmacopoeial work. It was pointed out 
how such a unification would aid in securing uniform analytical re- 
sults and in the interpretation of the different pharmacopoeias. 

The third set of resolutions, which were adopted after prolonged 
and thorough discussion, related to the control of antiseptics, with 
special reference to the securing of commercial honesty and the safe- 
guarding of the public. The congress expressed the opinion that 
such preparations should not be placed upon the market until they 
have been officially examined, both chemically and bacteriologically, 
and have received the approval of the departments of public health ; 
that their efficiency should be determined and the* claims made by 
the manufacturers be examined ; that the amount of their active 
ingredients and their bactericidal strength should be stated, and that 
the sale of those claiming to possess therapeutic properties and of 
those containing poisons the sale of which is legally restricted 
should be limited to pharmacists. 

The fourth resolution related to the introduction into the cur- 
ricula of schools of pharmacy of courses on the analysis of certain 



26 



Tenth International 



Collier ess. 



( Am. Jour. Pharm 

t January, 1911. 



physiological and pathological secretions, especially of that of the 
feces. It was pointed out in the discussion that such work prop- 
erly comes within the province of the pharmacist as a chemist and 
that it makes another professional bond between him and the 
physician. 

The fifth resolution related to the preparation of galenicals by 
pharmacists. The latter were urged to make these preparations 
themselves as far as possible. 

In addition to the formal reports a number of important scientific 
communications were made, some of which led to the adoption of 
further resolutions. Thus, as the result of a communication by 
Moller, it was resolved to advocate the adoption as an international 
standard of colors the standard of Klinchsieck and Valette. A 
paper by Hercod led to the adoption of a resolution in favor of the 
appointment of an international commission to establish a method 
for the standardization of pharmacopoeial preparations of pepsin and 
for establishing a standard strength for this product. 

A resolution was also passed expressing the opinion that it is 
desirable for the committees on pharmacopoeial revision to publish 
each year supplements calling attention to the real scientific advances 
made. 

Among the notable contributions made in the scientific section 
the following may be mentioned : Perrot, on the preservation of 
important plant drugs by the destruction of the intracellular 
enzymes ; Leger, on the constitution of the aloins ; Bourquelot, on 
glucosides ; Goris, on plants containing caffeine. 

The first of the resolutions presented by the section on profes- 
sional interests related to the control of the sale of specialties. The 
basis for the discussion of the subject, which was prolonged and 
animated, was the very comprehensive report prepared by Breugel- 
mans, Daminet, and Staes in which was reviewed the legislation on 
the subject in the leading countries of the world. Although the 
difficulties and complications which have arisen from the great in- 
crease in the number of such preparations and the problem resulting 
from the competition of manufactures were recognized, the discus- 
sion was limited largely to the phases which more directly concern 
the commercial side of pharmacy and especially to the subject of 
price protection. It was recognized that this is a question whi^^h 
will have to be solved by each country, but certain general principles 
were proposed, and the congress expressed the opinion that the sale 



Ain. Jour. Pharm. ) 
January, 1911. j 



Pharmacopoeia of Russia. 



27 



of medical 'specialties should, in all countries, be reserved to the 
pharmacists. 

The second resolution presented by the section on professional 
interests related to the formation of an international pharmaceutical 
federation having for its purpose the protection of pharmacy as a 
profession and as an applied science. It was decided to appoint a 
commission to prepare a constitution for such a federation and to 
accept an invitation from the government of Holland to make The 
Hague its headquarters. 

The third resolution related to the representation on pharmaco- 
pceial commissions of practical pharmacy, and the fourth to the limi- 
tation of the number of pharmacies. 

It was also resolved to make the question of patents and trade- 
marks one of the subjects for discussion at the next international 
congress of pharmacy. 

In addition to the scientific programme, visits were made to the 
exposition, where the chemical and pharmaceutical exhibits of differ- 
ent countries were explained, and to dairies devoted to the produc- 
tion of milk for infants. 

The members of the congress were the recipients of the most 
generous hospitality on the part of the officers of the congress 
and the pharmacists of Belgium. 



THE PHARMACOPCEIA OF RUSSIA. 

By M. I. WiLBERT, Washington, D. C. 

The new, sixth edition, of the Russian Pharmacopoeia, published 
in 1910, is undoubtedly one of the more interesting books of its 
kind and it is perhaps unfortunate indeed that its appearance only 
in the Russian language makes it comparatively inaccessible to much 
the greater number of American Pharmacists. Fortunately, how- 
ever, the official titles are Latin and the numerals in the formuke 
are Arabic. 

The general appearance of the book is all that could be desired ; 
it is neatly bound and excellently well ])rinted on a good quality of 
paper, and would generally be accepted as a thoroughly modern, 
up-to-date publication. 

The book contains a total of XVIII and 591 pages with descrip- 



28 



PJiannacopana of Russia. 



( Am. Jour. Pharm. 
\ Jiiniiarv, 1911. 



tions of 617 official articles. The official articles include 162 botani- 
cal drugs, 15 drugs of animal origin, 195 chemical substances, 218 
pharmaceutical preparations and 27 general descriptions. 

The general descriptions are unique in that they include not alone 
general descriptions of types of pharmaceutical preparations but also 
descriptions of parts of plants, such as seeds, flowers, leaves and 
roots. 

The Latin nomenclature has much in common with that found 
in the German Pharmacopoeia, the new French Codex and the new 
Swiss Pharmacopoeia so that there is even here a promise that the 
future will bring with it a proximation to international uniformity 
so far as the Latin names of widely used substances are concerned, 
even if it is, perhaps, LTtopian to expect that we may yet have 
absolute uniformity. 

Another indication that bodes well for the closer approximation 
of the several national pharmacopoeias is the fact that this edition 
of the Russian Pharmacopoeia like the ninth edition of the 
Swedish Pharmacopoeia and the new third edition of the Italian 
Pharmacopoeia was prepared in advance of the usual time of revision 
for the sole purpose of including the provisions of the Brussels' 
Conference Protocol. 

The agreement adopted at the Brussels Conference for the unifi- 
cation of pharmacopoeia] formulcX for potent medicaments is re- 
printed entire in the prefatory pages to the book, and the provisions 
appear to have been generally adopted in all of the formulas included 
in the body of the pharmacopoeia itself. 

Among the titles representing the newer additions to our materia 
medica we find: .T:thylum bromatum. Agar- Agar, Ammonium sulfo- 
ichthyolicum, Ammonium sozojodolicum, Antipyrinum, Chinosolum, 
Diuretinum (Theobrominum-natrio-salicylicum) , Heroinum, Hero- 
inum hydrochloricum, Phenacetinum, Salipyrinum, Salolum, Serum 
antidiphthericum, Sulfonalum, and Vaselinum. 

Many of these titles illustrate the difficuUies that we will be 
obliged to contend with for many years to come in developing 
names that are universally acceptable or applicable, because of the 
widely varying practices in connection with trade names and the 
protection given to individuals, in different countries, by laws gov- 
erning trade-marks. 



Am. Jour. Pharm. > 
Jauuaiy, 1911. j 



Book Reviezvs. 



29 



Chemical tests and assay processes have been given considerable 
attention and 33 pages are devoted to an enumeration of the reagents, 
volumetric solutions, and chemical apparatus necessary to apply the 
several official tests. 

An appendix contains a number of tables including a list of 
potent medicaments, table of maximum single and daily doses, table 
of specific gravity of official liquids, and an alcohol table giving the 
per cent, of alcohol by weight and by volume of mixtures of 
alcohol and water at 15° C. 

A double column index covering 32 pages completes a book that 
promises to be more than a passing factor in developing pharmacy 
in the country of its origin and will no doubt contribute much 
toward developing international unification of standards for potent 
or widely used medicaments. 



BOOK REVIEWS 

Abstract of Proceedings, United States Pharmacopceial 
Convention, 19 10. Compiled and edited by the Secretary of the 
Convention. Published by the Board of Trustees, November 30, 
1910. 

Pharmacists and others who are interested in the Pharmacopoeia 
of the United States will welcome this somewhat belated authorita- 
tive report of the United States Pharmacopceial Convention, pri- 
marily because of the information it contains, but also because it 
provides, for ready reference, a comprehensive and authentic account 
of the strenuous sessions of the Convention held in the City of 
Washington, in May, 1910, to provide for the revision of the 
Pharmacopoeia of the United States now in force. 

This abstract of the proceedings constitutes an octavo pamphlet 
of no pages, and in addition to a rather complete account of the 
actual happenings, presents verbatim reproductions of the several 
addresses and the reports of officers of the convention. In addition 
to the proceedings the pamphlet also contains : 

1. A financial statement covering all of the receipts and expendi- 
tures during the period, from May, 1900, to May, 1910. 

2. The Constitution and By-laws as revised by the Convention of 
1910. 



30 



Book Reviews. 



( Am. Jour. Phartn, 
\ Jiuuiiuy, 1911. 



3. The official list of members of the U. S. Pharmacopoeial Con- 
vention of 1910. 

This latter list is particularly interesting- in view of the unques- 
tioned ruling of the Chair : " That anyone elected a delegate here, 
who has not come, is not a member of this Convention, cannot be 
elected a member of any Committee, nor as an officer." 

To all intents and purposes this ruling limits membership in the 
Convention and official participation in the conduct of its affairs 
during the decennium to accredited delegates actually in attendance 
at the Convention. 

Because of the information that it contains, this pamphlet should 
be widely distributed and should be frequently consulted by all who 
are interested in the Pharmacopoeia of the United States and the 
development of its objects and its uses. M.I.W. 

Hygienic Laboratory Bulletin No. 70. A Study of Melting- 
point Determinations, with special reference to the melting-point 
requirements of the Pharmacopoeia. By George A. Menge, Wash- 
ington, Government Printing Office, 1910, p. loi. 

This Bulletin is essentially a report on progress of a study of 
melting-point determinations made for and in co-operation with the 
Committee of Revision of the Pharmacopoeia of the United States, 
and constitutes perhaps the most comprehensive review of this factor 
that has as yet been published, from a pharmaceutical point of view. 

The various causes for divergence in the melting-point inter- 
pretations are reviewed and illustrated. The author also illustrates 
and figures the necessary appliances for a comparatively simple 
method that appears to be well adapted to present pharmacopoeial 
needs. 

The experimental data reported includes melting-point determina- 
tions on 24 official substances and amply suffices to show the need 
for adopting a definite and uniform method and procedure for de- 
termining the melting point of official substances if this factor is to 
be accepted as an indication of the identity or purity of official 
substances. 

Pharmacists and chemists who are interested in pharmacopoeial 
tests and requirements will find much in this Bulletin to assist 
them in determining the probable value of melting-point determina- 
tions in connection with official chemicals. 



Am. Jour. Pharm. ) 
January, 1911. J 



Book Reviews. 



31 



Copies of the Bulletin may be had on application to the Surgeon- 
General, U. S. Public Health and Marine-Hospital Service, Wash- 
ington, D. C. 

The Microscopical Examination of Foods and Drugs. A 
practical introduction to the methods adopted in the microscopical 
examination of foods and drugs, in the entire, crushed and pow- 
dered states. By Henry George Greenish, F.I.C., F.L.S., Pro- 
fessor of Pharmaceutics to the Pharmaceutical Society of Great Brit- 
ain and Director of the Pharmacy Research Laboratory. With 229 
illustrations. Second edition. Philadelphia : P. Blakiston's Son & 
Co., 1012 Walnut St., 1910. $3.00 net. 

Professor Greenish is well known as an author of several stand- 
ard works and a number of excellent papers. The present work is 
a laboratory manual, treating of the general technic employed in the 
microscopic examination of vegetable drugs and food products and 
giving a fairly large number of typical examples under each of the 
classes considered. There are some 15 sections, in which are con- 
sidered: starches, hairs and textile fibres, spores and glands, ergot, 
woods, stems, leaves, flowers, barks, seeds, fruits, rhizomes, roots, 
adulterants of powdered foods and drugs and a general scheme for 
the examination of powders. 

While the work is especially written for the students of the 
School of Pharmacy of the Pharmaceutical Society of Great Britain, 
it could be well adapted by teachers in other schools and colleges of 
pharmacy in their work. The following statement from the 
preface is deserving the attention of the teachers in those 
schools of pharmacy where the subject of pharmacognosy is 
not taught as a means to a practical end. " Before the microscopical 
examination of vegetable foods and drugs can be intelligently prac- 
tised, a general knowledge of botany and a fairly sound and thor- 
ough acquaintance with botanical histology are absolutely necessary. 
It is as impossible for anyone to become a competent microscopist 
without such preliminary knowledge, as to become a competent 
analytical chemist without first acquiring a sound knowledge of the 
theory and principles of the science of chemistry. For this reason 
it appears to me that the training now given in the School of Phar- 
macy of the Pharmaceutical Society, comprising as it does, a knowl- 
edge of the principles upon which the sciences, of botany and chemis- 



32 



Susan Hayhtirst. 



( Am. Jour. I'ljann. 
\ Jiuniiiiy, 1911. 



try rest as well as training in the application of the knowledge thus 
acquired, is admirably adapted to fit a man to become an expert 
not only in the microscopical, but also in the chemical examination 
of foods and drugs." Again and again is one reminded in this 
work of Greenish's of the observation of Hassall in regard to the 
application of the microscope " that there is scarcely a vegetable 
article of consumption, not a liquid, which may not be distinguished 
by means of that instrument. Further, that all those adulterations 
of these articles which consist in the addition of other vegetable 
substances and which constitute by far the majority of the adultera- 
tions practised, may likewise be discovered and discriminated by the 
same process." Furthermore, Greenish calls attention to the fact 
that the " Investigations recently conducted by the Society at the 
request of the General Medical Council have also shown that the 
microscopical examination of powdered drugs yields results of far 
greater value in determining their identity and purity than such 
chemical data as the amount of ash yielded by them." In view 
of the splendid work done by Greenish this work will do much 
in making a rational consideration of the subject of pharmacognosy 
possible and cause students and pharmacists to be willing to devote 
a sufficient amount of time to the mastery of the principles involved 
in the work. 



SUSAN HAYHURST. 

The memorial exercises, held at the Philadelphia College of 
Pharmacy on November 15, 1910, in connection with the presentation 
to the college of a portrait of Dr. Susan Hayhurst, were a worthy 
tribute to this pioneer woman pharmacist, to whom the 
majority of the women graduates of the Philadelphia College of 
Pharmacy are indebted for the opportunity she gave them to acquire 
a knowledge of the practical side of pharmacy. 

Dr. Hayhurst matriculated in the Philadelphia College of Phar- 
macy in 1879, at the age of 59, and graduated four years later. 
During her more than thirty years of service as apothecary of the 
Woman's Hospital of Philadelphia she gave employment to some 
sixty-five young women, a number of whom were present on this 
occasion and contributed to the testimonial held in honor of prob- 



Am. Jour. Pharm. \ 
January, 1911. / 



Susan Hayhurst. 



33 



ably the first woman graduate to practise pharmacy in America if 
not the world.^ 

Shortly after the death of Dr. Hayhurst on August 7, 1909, some 
of the women graduates of the college, under the leadership of 
Miss Sarah L. Naly, her successor as apothecary of the Woman's 
Hospital, determined to have a portrait done in oil for presentation 
to the College. Early in November, 1909, they obtained the consent 
of the Board of Trustees to hang the proposed painting in the 
Museum of the College and soon thereafter the Committee of the 
women graduates secured the services of a Philadelphia artist, Miss 
Florence J. Newton, to execute the work. The portrait was made 
after a photograph of Dr. Hayhurst, taken but a few months before 
her decease by the well-known photographer, Mr. F. Gutekunst, 
assisted by the artist's personal recollection of her subject. A re- 
production of the photograph is given in the frontispiece. The 
painting is a most excellent one, being about two-thirds life-size, 
and hangs in a prominent place in the Museum, selected by the 
women graduates. 

The president of the College, Mr. Howard B. French, presided 
at the presentation exercises, and in opening the meeting referred 
to the splendid services of Dr. Hayhurst for the advancement of the 
Woman's Hospital of Philadelphia, and spoke of his personal knowl- 
edge of her work for the benefit of women in pharmacy and her 
noble example to her students and apprentices. 

Professor Remington was to have presented the portrait on 
behalf of the women graduates, but was unavoidably absent and his 
address was read by Professor Kraemer. It was as follows : 
Mr. Howard B. French, 

President of the Philadelphia College of Pharmacy : 

On behalf of the women graduates of the Philadelphia College 
of Pharmacy, we have much pleasure in presenting to the College this 
portrait of Susan Hayhurst, M.D., Ph.G., who was the first woman 
graduate of this College. 

The long and useful career of our deceased friend was marked 

^ Elizabeth Marshall, though not a graduate in pharmacy, was probably 
the first woman to practise pharmacy in this country (see this Journal^ 
1904, p. 271), and it is recorded that Dr. Mary Putnam Jacobi graduated 
from the New York College of Pharmacy in 1883, the year of Dr. Hay- 
hurst's graduation, but it is probable that she never engaged in the practice, 
having become distinguished as a teacher and practitioner in medicine. — Editor, 



34 



Snsa)i Hayhurst. 



( Am. Jour, rharm. 
( Jauiiary, 1911. 



by many acts of kindness and she made the path easy for many a 
struggHng woman, striving for the coveted diploma of her Alma 
Mater. Dr. Hayhurst graduated from the Woman's Medical Col- 
lege in 1857 from our College in 1883. 

In her position as apothecary of the Woman's Hospital, she 
had the opportunity of giving practical instruction to girls who had 
chosen pharmacy for a vocation and her labors were more than 
appreciated, because for many years the dispensary of the Woman's 
Hospital was the only place where girls could secure practical knowl- 
edge of the business, owing to the prejudice which existed some 
years ago against women pharmacists. 

As a student, Dr. Hayhurst was diligent in her efforts to acquire 
pharmaceutical knowledge. Until within the last few years of her 
life, she could be found poring over books and freely giving to her 
associates and younger women the information which she had ob- 
tained. vShe became a veritable mine of practical points. 

Her disposition was kindly, yet when occasion required, she could 
express herself forcibly, particularly when some of the women would 
neglect some duty or commit, as she would say herself, " a pharma- 
ceutical crime." 

It is rarely given to any one to spend thirty odd years in teaching 
pharmacy but Dr. Hayhurst has this distinction, and it will be many 
years before her record of earnest, helpful, devoted service will be 
equalled. She was loyal to her Alma Mater to the last and she 
never tired of singing the praises of her beloved College. 

To the women and girls who have had the benefit of her instruc- 
tion the example of her beautiful life of service must be an inspiration. 
Gentle but firm, steadfast and unyielding in her devotion, she has 
gone on before, and Mr. President we now offer to you as the repre- 
sentative of this College, this portrait, believing that you will cherish 
it and give it a place among the portraits of those honored ones, 
who have testified their allegiance to the oldest and best College 
of Pharmacy in America. 

In accepting the portrait, Mr. French said that it gave him great 
pleasure as president of the College to receive the portrait of Dr. 
Hayhurst and that it would find a place among the portraits of other 
leaders in American pharmacy on the walls of the College. He 
expressed his appreciation of the loyalty of the women graduates 
to their Alma Mater, and then called for the reading of a biographi- 



Am. Jour. Pharm. ) 
January, 1911. | 



Susan Hayhurst. 



35 



cal sketch of Dr. Hayhurst by Miss Susannah G. Haydock, which 
will be pubHshed in the Alumni Report of the College. Additional 
remarks were made by Miss Naly, Dr. Anna E. Broomall, Mr. 
Charles C. Parsons, Mr. E. M. Boring, Prof. C. B. Lowe and 
Professor Kraemer. 

The following sketch of Dr. Hayhurst is prepared in large part 
from the data secured through Miss Florence Yaple from various 
of her friends and relatives, especially her nephew, Mr. Walter F. 
Hayhurst, a lawyer residing in Lambertville, N. J., and extracts 
adapted from a sketch by Miss Sue P. Chambers which appeared in 
Woman's Progress some years ago (January, 1895). 

Dr. Susan Hayhurst was a descendant of Cuthbert Hayhurst, 
a member and minister of Settle Monthly Meeting of Friends, in 
Yorkshire, England, who came to this country in the ship " Wel- 
come " with WilHam Penn ; he died the year following and was 
buried September 2, 1683. His widow, Mary, took up certain lands 
which were allotted to him in Middletown Township, Bucks County, 
Pa., near the present village of Langhorne. Four generations later 
her father, Thomas Hayhurst, was born in this neighborhood, 
and married Martha Croasdale, also of an old Quaker family; he 
was a man self-educated, but of considerable ability and many 
talents. He was a surveyor and scrivener. He afterwards moved 
with his family to Wilmington and Camden, Delaware, where he 
engaged in the manufacture of " earthenware," and later engaged 
in the commission business in Philadelphia. He also engaged in 
school teaching, and about the year 1840 with his son, Jeremiah 
Hayhurst, the father of Walter F. Hayhurst, already mentioned, 
kept a select school at West Chester, Pa. There were eight children 
in the family and Susan was the second, having been born December 
25, 1820, at Middletown, Pa. 

Her schoolgirl days were passed at an institution in Wilmington, 
under the influence of " Friends." As a student she was particu- 
larly apt in mathematics and could recite verbatim any amount of 
text. She would have been considered an apt pupil, but when she 
came to teach found the want of that technical training which she 
afterwards obtained by taking the best instructor available in what- 
ever study she wished to pursue. 

She commenced teaching when quite a young girl, her first school 
being in Bucks County, Pa., near Newtown, and spent some years 



36 



Susan Hay hurst. 



J Am. Jour. Phartn. 
1 Jamiivry, 1911. 



in various country schools — an important and interesting portion of 
her life, as much of her time was spent with a class of people inter- 
ested in the stirring events of that day, and many of them not lack- 
ing in intellectual culture. At one time she was a frequent compan- 
ion of a skilled botanist, and together they became acquainted with 
the wild flowers of field and forest and meadow. 

When her parents moved to Philadelphia, amongst her new ac- 
quaintances she found, in one of the professors of the Woman's 
Medical College, a very superior teacher of chemistry. To avail 
herself of Dr. Johnson's instruction, she entered the college for that 
and physiology, thinking to better qualify herself for teaching these 
branches. After some months' study, becoming deeply interested, 
she decided to take the entire medical course. To do this it was 
necessary to teach in the summer while attending lectures in the 
winter. Again she went to the country, where she found liberal- 
minded people and a devoted botanist. There she and her medical 
books were curiosities. 

The last year of her course at college she was induced to take 
charge of the Friends' School at Fourth and Green Streets, Phila- 
delphia, and was principal of that school when she graduated in 
medicine in 1857. 

That graduation day would contrast greatly with one from the 
same college at this time. The medical woman of to-day knows 
little of the social ostracism that attended the pioneers in this pro- 
fession. Now unnoticed in the crowd, or respected and even hon- 
ored whenever they come to the front ; in past days, even on the 
street, they were subject to indignities from their fellow students 
of other medical colleges. The commencement (numbering ten can- 
didates) was a quiet affair, with a few friends who were brave enough 
to stand by those, who, better than they then knew, " were paving 
the way for liberal education." On this occasion. Prof. C. D. 
Cleveland, the writer on English Literature, then president of the 
college, came forward and stated that he had sought in vain in 
this city for a reverend who would take part in the services, and 
then himself — a layman — asked the Divine blessing on these young 
women who were about to enter an almost untried field. 

Dr. Hayhurst still continued ten years at Fourth and Green 
Streets, then opened a school of her own with a class of fifty, many 
of whom had been her former pupils. 



Am. Jour. Pharm. I 
January, 1911. j 



Susan Hayhurst. 



37 



We next find her going West for a much-needed rest and change, 
and to visit friends. Then she was asked to organize a new pubUc 
school in the town she was visiting, on the Philadelphia plan. Hav- 
ing finished this work and made the visit/ she at the end of a year 
returned to Philadelphia, and with the intention of taking up the 
practice of medicine, entered the Woman's Hospital to familiarize 
herself with the advance ideas in medicine since her graduation. 

She was solicited by the management of the hospital to take 
charge of its pharmaceutical department, a position of great respon- 
sibility, and entered on her new duties in 1876. 

With her life-long habit of knowing — what may be knovvu — 
of the subject in hand, and having turned away from that which she 
had intended as a life work, she again took up the student life in 
connection with daily service as pharmacist at the hospital. It was 
not her habit to leave anything undone in the way of investigation 
that could add to her efficiency, so she sought and obtained per 
mission to matriculate at the Philadelphia College of Pharmacy. 

No difficulty surrounded her attendance of these lectures. The 
boys were probably not glad to receive this one woman who entered 
a class heretofore occupied entirely by men, and who might mar 
their college freedom, but they made no offensive demonstration. 

When she took her tickets it was a question whether the college 
would grant her its diploma, but on the completion of its course, she 
was graduated in 1883. 

Professor Remington, in his valedictory address, said : " It is the 
best and largest class we have ever graduated, and we do what has 
never been done in the history of these sixty-two commencements, 
confer the degree on a woman." Then arose such a storm of 
applause as would have satisfied the most ambitious debutante. 
The large hall was filled in every part, and the graduates, 150 in 
number, seemed to vie with the audience in expressing their gratifi- 
cation. 

The contrast in twenty-six years between these two commence- 
ments in which Dr. Hayhurst participated marks the advance of pub- 
lic sentiment. At the first when it was an innovation for women 
to enter the medical world, there were but ten graduates, a small 
audience, and no enthusiasm. A wide acquaintance with medical 
students made lier influence far-reaching. From India, Cliina and 
Japan came messages, gifts of rare and beautiful things, thanks 



38 



Susan Hayliiirst. 



/Am. Jour. Pharm. 
t January, 1911. 



for advice given, for supplies of all kinds selected. Many a mis- 
sionary owed the successful equipment for her work to this kindly 
care, either before she went or in answer to requests after she 
arrived in the foreign country. The purchase and manufacture 
of supplies for her own department in the hospital passed under 
Dr. Hayhurst's supervision, " and a care " at times was extended 
to matters not connected with drugs. To have seen her with ham- 
mer and screw-driver in hand one might have wondered if she 
possessed any of the characteristics of that ancestor who had " a 
very good mechanical head," according to his neighbor and friend, 
the one time Governor of New Jersey. All this busy life, yet it did 
not prevent an every summer devotion to a flower garden which 
furnished many a bouquet for friend and invalid, nor the taking 
up of a new study, or the critical pursuit of an old one. 

Her reading was very wide, and she read very much poetry and 
fiction for her personal pleasure, but seemed to read science and 
history with quite as much satisfaction. Her method of thought 
was logical and she was interested intensely in all the questions of 
the day. She believed in Woman Suffrage, although not taking 
much active part in the movement, and sometimes regarding with 
amusement the methods of some of its advocates. She was intensely 
interested in the abolition of slavery, and afterwards in the eleVation 
of the colored people. She was a consistent member of the Society 
of Friends and a regular attendant at meeting, although seldom 
taking any active part in the business. 

It is stated that she met William Loyd Garrison, Wenclel Phil- 
lips, the Burleighs, Lucretia Mott, and many other prominent anti- 
slavery advocates. In later years she was particularly intimate with 
Anna Jeans, the Phihdelphia philanthropist and was consulted by 
her in the distribution of her charities. 

In enumerating Dr. Hayhurst's activities reference should also 
be made to the fact that .she was taught surveying by her father 
and that she assisted him in this line of work. Latterly her whole 
interest was centred in the Woman's Hospital; in addition to the 
duties of her regular position, she was frequently consulted by the 
managers and took an active part in raising funds for many im- 
provements. She was particularly cheerful in her manner and 
enjoyed a joke. An incident is cited that when they were celebrat- 
ing the Silver Anniversary " of her employment at the hospital 



Am. Jour. Pharm. ) 
January, 1911. J 



Susan Hayhurst. 



39 



some newspaper man wanted her age and she refused to give it. 
Afterwards she said that the reason she refused was the fear that 
the people would think she was getting too old to take an active part 
in business. 

Dr. Hayhurst possessed marked social qualities, and was a 
member of the following societies : The Century Club, of which she 
was a charter member; The New Century Guild (both women's 
clubs) ; The Browning Club of Philadelphia, in which, however, her 
membership cannot be confirmed by the present secretary; The 
American Academy of Political and Social Science ; The Woman's 
Suffrage Society of Philadelphia, and The Pennsylvania Pharma- 
ceutical Association. 

She was a good disciplinarian, and during all the years of her 
charge of the dispensary of the Woman's Hospital it was character- 
ized by cleanliness, neatness and orderliness in every part. Not 
only this, she provided ample equipment in the way of pharmaceuti- 
cal apparatus and always sought to use the most approved methods 
in the making of preparations, the majority of which were made 
by her assistants. She also considered it a part of her duty to look 
into the qualities of new remedies, and it is to her credit that 
very few, if any, of the fraudulent or worthless preparations offered 
for sale.ever found their way into the dispensary of the Woman's 
Hospital. She always spoke of her assistants as my girls," and 
was ever mindful of their interests, both social and intellectual, fre- 
quently inviting them to accompany her to the meetings of the socie- 
ties of which she was a member. 

At a meeting of the Board of Managers of the Woman's Hos- 
pital, held September lo, the following resolutions were offered: 

Resolved, That in the death of our valued Friend. Dr. Susan 
Hayhurst, the hospital has lost a faithful and devoted worker ; 
therefore 

Resolved, That the thirty-three years spent in our midst will 
long be remembered by us, and her influence be felt, especially in 
the department over which she presided ; the aim of her life was to 
further the interests, and widen the influence of the hospital, and 
by her faithfulness to this duty, she showed her love for it. While 
we miss her presence, we know that " our loss is her everlasting 
gain." Therefore, 

Resolved, That a copy of these resolutions be entered on the 
Minutes of the Board, and a copy sent to the family. 



40 American Phaniiaceiitical Association. / Am. jour. pharm. 

^ ( January, 1911. 

THE CITY OF WASHINGTON BRANCH OF THE AMERI- 
CAN PHARMACEUTICAL ASSOCIATION. 

The regular stated meeting- of the City of Washington Branch 
of the American Pharmaceutical Association was held at the Hotel 
Raleigh on the evening of November ii, 1910, with the members of 
the Association of Official Agricultural Chemists as guests. 

The subject under discussion was The Pharmacopoeial Conven- 
tion of 1910 and the prospective Pharmacopoeia of the United States. 

Dr. H. W. Wiley, the President of the United States Pharma- 
copoeial Convention, presented a communication in the course of 
which he outlined his opinions regarding the Pharmacopoeia and the 
methods to be followed in revising it. 

Prof. Joseph P. Remington, the Chairman of the Committee 
of Revision, expressed the opinion that the Convention was indeed 
fortunate in having Dr. Harvey W. Wiley as its president and pre- 
sented a short communication in the course of which he commented 
on some of the more important points referred to by Dr. Wiley and 
outlined the nature and amount of work that had been accomplished 
during the summer months. 

Commenting further on the scope of the Pharmacopoeia he ex- 
pressed the belief that the real sentiment of both physicians and 
pharmacists was neither in favor of a skeleton pharmacopoeia nor 
of a padded pharmacopoeia, l3ut of what he was pleased to designate 
as a sane pharmacopoeia. 

He then called attention to a prospective communication by Prof. 
Rusby, for the Asso-^iation of Official Agricultural Chemists, in 
which he points out the need for having a book of standards for all 
drugs that are widely used, so as to facilitate and simplify the work 
of the United States Custom House officials in connection with the 
importation of drugs. 

Prof. Remington also pointed out that for many years the 
Pharmacopoeia was a closed book to the medical profession because 
its members had been lead away from it by the detail man of the 
manufacturer and proprietarv medicine maker. The resulting decay 
of therapeutics has brought about a state of confusion and a tendency 
to therapeutic nihilism that he considers to be most unfortunate. 

He holds that physicians do not know a sufficient number of 
U.S. P. preparations and do not appreciate the fact that their fellow 
practitioners in different parts of the country, and in different cities, 



^ January iQif"' } American Pharmaceutical Association. 41 

use totally different medicines, for which the Pharmacopoeia of the 
United States should furnish standards. 

Prof. 1. V. S. Stanislaus, of Philadelphia, asserted that the paper 
by Dr. Wiley had been to him a revelation and a treat true and rare. 
He had been particularly impressed by the reference to needless 
duplication of drugs having similar properties and willingly endorsed 
the proposition to delete useless duplications from the Pharmaco- 
poeia. 

He pointed out that the content of previous pharmacopoeias 
represented the selection and dictates of the few and not of the many 
and expressed the hope that in the forthcoming Pharmacopoeia 
greater care be exercised regarding admissions and deletions. 

Dr. Murray Gait Hotter, the Secretary of the Pharmacopoeia! 
Convention, discussed a number of the more important points em- 
bodied in the able, comprehensive and timely paper by Dr. Wiley 
and pointed out more particularly that the work and the function of 
the Executive Committee, as outlined by Dr. Wiley, was in accord- 
ance with the intent and purpose of the Board of Trustees of the 
former Convention. 

He also pointed out that the professional representation on the 
General Committee of Revision was not alone interesting but rather 
sienificant. Of the total number 34 (indeed 35 when a vacancy was 
filled) were nominees of the pharmaceutical caucus and but 16 were 
nominees of the medical caucus. Of the latter it is also interesting 
to note that only 2 reached the executive committee. 

In connection with the scope of the Pharmacopoeia he pointed 
out t^iat the Pharmacopoeial Convention, by a vote of 95 to 47, 
emDhatically recorded its conviction that substances " whose value 
and use have not been established should not be included. And 
then, on the plea that it was unnecessary to hamper the Committee 
elected for the purpose of carefully selectino- the list of substances, 
the Convention was induced to strike out, bv a vote of 123 to 40, this 
" ambiguous and dansferous provision " thus leaving the final decis- 
ion rep-arding scope with the members of the General Committee 
of Revision. 

With reference to the business of the Pharmacopoeial Convention 
he Jtsserted that it had been pointed out by several observers that 
" the financial statement made to the Convention was in no wise 
satisfactory, explicit, or in iustice to the intelligence of the body 
to which it was delivered.'' Tn commenting on " the enormous sales 
of the book nmounting to nearlv 40,000 copies the first year," he 



42 American Pharmaceutical Association. { ^ ja^iTry iqT™' 

pointed out that as a matter of fact the sales of the Pharmacopoeia 
did not reach 40,000 until the middle of 1908. 

In concluding he expressed the belief that if those who are to 
ef¥ect the work of revision do not clearly realize their responsibility 
to the Convention and to the several professions represented, and 
produce a book of standards indeed, but of standards for substances 
of established value and use, the next Pharmacopoeia, instead of 
being- a force, will be a farce. 

Dr. Reid Hunt, Chairman of the American Medical Association 
Committee on the Pharmacopoeia of the United States, pointed out 
that regarding- the scope of the book there were two diametrically 
opposed views, both of which deserve consideration. The manufac- 
turer and the pharmacist desire to have a book of standards that 
will include all of the substances that are, have been, or may be 
used as medicine, while the medical practitioner desires to have 
a book of standards for the approved therapeutic agents only so 
that the book may be used as a basis for instruction in medical 
schools and as a guide to the physician who is willing to adopt and 
use recognized standard remedies. It must be evident that these 
two objects are so totally different that it would be practically im- 
possible to agree on a compromise and any attempt to do so would 
be considered a straddle that would be acceptable to but few. 

He heartilv endorsed the stand taken by Dr. Wiley regarding 
the scope of the book and expressed the belief that physicians and 
pharmacists should not be expected to furnish standards for Custom 
House offi^^ials and patent medicine manufacturers. As chairman 
of the Committee on the Pharmacopoeia of the American Medical 
Association he had been able to get into communication with thou- 
sands of medical practitioners in various parts of the United States, 
all of whom were willing to use the best medicines that were avail- 
able and desirous of obtaining authentic information regarding the 
probaWe efficiency of drugs. 

Dr. Hunt outlined the methods that had been emploved by his 
committee to secure the co-operation of the several sections of the 
American Medical Association, and referred more especially to the 
correspondence that had been had with medical men in active 
practice who were also teachers of materia medica and therapeutics 
in mediral schools and colleges, and asserted that despite the fact that 
the evidence thus secured had been submitted through the Pharmaco- 
poeial Convention to the Committee of Revision, many of the mem- 
bers appeared to be willing to ignore the wishes of physicians and 



^ January 191 ™" } AmeHcan Pharmaceutical Association. 43 

the indications are that the scope of the forthcoming Pharmacopoeia 
will again represent the views of but a limited number of individuals. 

As an indication of the opinions held by the better informed 
medical men he quoted Dr. Abraham Jacobi, the Nestor of American 
physicians, who in discussing the content of the present Pharmaco- 
poeia deplored the fact that the makers of the Pharmacopoeia were 
not willing to restrict the book to the best remedies only. 

Dr. W. M. Barton seconded the remarks made by Dr. Hunt and 
asserted that he had also come to the conclusion that there are two 
diametrically opposed opinions regarding the scope of the Pharmaco- 
poeia and was satisfied that the book cannot, as it now stands, be 
accepted by medical men as a guide. He suggested the possibility 
of limiting the medical recognition of drugs by introducing a fair 
statement of the physiological action of the substance with each 
description. 

Dr. Wiley, in closing the discussion, expressed himself satisfied 
with the feast of oratory that had been supplied to the members of 
the Cit}^ of Washington Branch and their guests, and felt sure that 
nothing that he could add would tend to increase the appreciation 
of the importance of revising the Pharmacopoeia of the United States 
along the lines laid down by the United States Pharmacopoeial 
Convention. M. T. Wilbert, Secretary. 

REPORT OF THE CITY OF WASHINGTON BRANCH, COMMITTEE ON THE 
JOURNAL OF THE AMERICAN PHARMACEUTICAL ASSOCIATION, 

Your Committee, appointed to consider the paper by Mr. Joseph 
W. England entitled The Journal of the American Pharuiaceutical 
Association," greatly regrets to announce that, since its appointment 
at the October meeting of this Branch, the American Pharmaceutical 
Association has sustained a serious and irreparable loss in the death 
of Prof. C. S. N. Hallberg, the editor of the Bulletin and the chief 
Editor-elect of the proposed journal. This untimely death greatly 
complicates the problems involved in the launching of the new 
journal. While your committee was not specifically instructed to 
consider anytliing but tlic communication above referred to, it 
nevertheless feels that the occasion is an unusual one and that the 
late Editor's long years of disinterested service to pharmacy, and 
particularly the American Pharmaceutical Association, merit special 
recognition. 

Your Committee would, therefore, respectfully recommend the 
adoption of the following preamble and resolutions : 



44 American Pharmaceutical Association. / Am. jour. Pharm. 

^ ' ( January, 1911. 

Whereas, We, the members of the City of Washington Branch 
of the American Pharmaceutical Association, having learned of the 
death of C. S. N. Hallberg, a prominent member, and Editor of the 
Bulletin of our Association, are desirous of expressing our apprecia- 
tion of his long continued and unselfish interest in everything per- 
taining to the advancement of the American Pharmaceutical Associa- 
tion and the progress of true pharmacy generally, now, therefore, 
be it 

Resolved, That we hereby record our appreciation of his unfail- 
ing and untiring devotion to pharmacy, his singleness of purpose, 
and the unquestioned probity which guided his every effort in secur- 
ing for true pharmacy the recognition properly due it. 

Resolved, That a copy of these resolutions be embodied in our 
minutes and a copy forwarded to the family of the deceased as an 
expression of our sympathy and esteem. 

The evidently authoritative communication, entitled " The Jour- 
nal of the American Pharmaceutical Association," published in the 
October, 1910, number of the Am. Ph. A. Bulletin (p. 555), indicates 
that there are a number of important questions which appear, as 
yet, to have received insufficient consideration by the Committee 
therein referred to. 

By far the most important of these several questions is the 
vacancy caused by the unexpected death of the newly elected Editor- 
in-chief. Professor C. S. N. Hallberg was generally conceded to 
be thoroughly well-fitted by his unusual training and experience to 
undertake the launching of this project, so fraught with possibilities 
for success or failure, for progress or retrogression, as the publica- 
tion of a journal which will, inevitably, bring the Association into 
active competition with a number of drug and trade journals which 
have for decades been more or less influential in maintaining and 
developing the Association along the lines hitherto pursued. 
. That the position of Editor-in-chief and general manager of such 
a Journal is recognized as being the all-important factor, on which 
the success or failure of the enterprise must depend, is well indicated 
by the following opinion of a correspondent, himself well qualified 
by long years of experience to speak with authority: 

" What the American Pharmaceutical Association needs is a man 
who has arrived, who understands every phase of journalism from 
the buying of paper and keeping tabs on the printer-man, all the 
way through soliciting " ads," preferred positions, writing top-heads 
and sub-heads, making up a page of reading matter in an artistic 



Am. Jour. Pharm. ) American Pharmaceutical Association. 4s 

January, 1911. j ~-' 

manner, and so forth, all the way down to hiring and firing help 
and standing off the dissatisfied co-boss and the cantankerous adver- 
tiser or contributor. Such a man is rare and is nascitur nan fit, and 
he has yet to go through a course of training to develop his technic 
at that." 

The importance of this one question alone, the imperative need 
of securing for the prospective Journal an editor who is independent, 
efficient, fearless, and competent, would appear to your committee 
to be a sufficiently valid reason for deferring the publication of the 
new Journal from July i, 191 1, to January i, 1912, so as to give 
the members of the Council of the Am. Ph. A. ample opportunity to 
canvass all of the several candidates, and to select from among them 
the one man most capable of meeting the requirements so tersely 
outlined above. 

In addition to this self-evident reason for delaying the publica- 
tion of the initial number of the proposed Journal, your committee 
would point out that there are a number of other reasons, any one 
of which should suffice to cause the Council of the Am. Ph. A. seri- 
ously to consider the advisability of deferring publication of the 
Journal until after the meeting of the American Pharmaceutical 
Association, in August, 191 1. In order that this report may not 
exceed reasonable limits, but a few of these reasons may be men- 
tioned and they but briefly : 

For very practical reasons, it is advantageous to begin and end 
a volume of a periodical with the calendar year. The importance 
of this consideration is, perhaps, best appreciated by librarians and 
compilers, but even the casual reader must recognize the possibility 
of irritating mistakes and serious delays caused by incomplete refer- 
ences to articles in journals covering a portion of two calendar 
years. 

The outline of the scope of the prospective Journal, as presented 
for the committee in the article referred to your committee, is alto- 
gether too general to be seriously considered by any association hav- 
ing the ideals and the aims of the American Pharmaceutical Associa- 
tion. The scope of the Journal, as thus outlined, would permit of a 
vacillating policy on the part of the editor or the committee on publi- 
cation, both as to the reading matter and as to the kind and character 
of the advertising matter that is to be accepted. 

In the opinion of your committee, the Council of the Association 
should also define the responsibility for material appearing in the 
reading pages of the Journal. We would suggest that it require 



46 American Pharmaceutical Association. {^j.;,f°ary Tyn""' 

that all articles be signed, unless full and complete responsibility be 
assumed by the editor-in-chief. Such a policy would obviate pos- 
sible misunderstandings and be a safeguard against anonymous 
communications. 

Your committee would call attention to the proposed change in 
the size of the publication, as outlined in the paper under discussion. 
For upwards of fifty years the publications of the American Pharma- 
ceutical Association have been in the widely used and convenient 
octavo form. The proposed change to quarto would necessitate re- 
arrangement, and probably cause dissatisfaction in every Hbrary in 
which the publications of the Association are kept on file. Apart 
from the possible factor of economy, there is nothing whatever to 
recommend this proposed change. 

Your committee would also beg leave to call attention to the fact 
that there appears to have been no provision made for publishing 
the report on the progress of pharmacy for the period between 
July I, 1910, and June 30, 191 1. We would recommend that this 
matter be published as a separate volume, in size uniform with the 
present bound volumes of the " Proceedings." We would recom- 
mend further that, for the period after July i, 191 1, this report be 
embodied in the Journal itself, so as to enhance the current value 
of the pubhcation as much as possible. 

Regarding the beginning of the publication on July i, 191 1, as 
heretofore decided upon, your committee would point out that the 
general scarcity of desirable original material in July would seriously 
militate against launching the Journal in the most presentable form 
at this time of the year, and would tend to hamper its influence by 
prejudicing both members of the Association and non-members at 
the very outset. On the other hand, we would point out that, in 
the event that the publication be deferred until after the annual 
meeting of the Association, the present Bulletin could be continued 
for all necessary announcements and news reports, and the initial 
numbers of the Journal be prepared in advance, so as to provide for 
the early publication of the original articles presented at the next 
annual meeting — even if it should be found necessary materially to 
enlarge the earliest numbers of the Journal, this would create a 
favorable impression. 

To recapitulate, your committee heartily agrees with the senti- 
ment that: 

" In deciding to establish a Monthly Journal, the American 
Pharmaceutical Association has taken one of the most important 



Am. Jour. Pharm. ) 
January, 1911. j 



New Essential Oils. 



47 



steps in its history, a step potential witli large possibilities of good 
for American pharmacy." 

It should be remembered, however, that in the event that this 
Journal should not prove to be all that its most ardent advocates 
expect it will be, but becomes an additional factor in hindering 
progress, instead of promoting the objects of the American Pharma- 
ceutical Association, as paraphrased so tersely from the late Editor 
of the Bulletin, such a Journal might serve to stifle research, sup- 
press knowledge, and discredit pharmaceutical education. 

Your committee would, in conclusion, reiterate its original recom- 
mendation, that the Council of the American Pharmaceutical Asso- 
ciation be importuned to defer publication of the Journal until oppor- 
tunity shall have been afforded for the thorough discussion of these 
considerations. 

In view of the urgent and far-reaching importance of this matter, 
your committee would recommend that the Secretary of the Branch 
be directed to forward copies of this report to the individual members 
of the Council of the American Pharmaceutical Association and to 
the pharmaceutical press. 

Respectfully submitted, 

(Signed) Lewis Flemer, 

H. E. Kalusowski, 
S. L. Hilton, 

Dec. 10, I9IO. M. I. WiLBERT. 

The above report was unanimously adopted at the meeting of 
the City of Washington Branch of the American Pharmaceutical 
Association, held on the evening of Saturday, December lo, 1910. 

In accordance with the instructions contained therein, I am send- 
ing you this copy. Respectfully, 

M. I. WiLBERT, 

Washington, D. C, Dec. 17, 1910. Secretary. 



NEW ESSENTIAL OILS.* 

Oil of Xanthoxylum alatum. From London we received 
under the name of Chinese Wild Pepper " the fruit of Xanthoxylum 
alatum Roxb., a shrub belonging to the Rutacese, which occurs in 
the mountains of Northern Bengal as well as in China. Upon dis- 

* From the Semi- Annual Report of Schimmel & Co. (Fritzsche Brothers), 
October, 1910. 



48 



New Essential Oils. 



( Am. Jour. Pbarm 
( January, 1911. 



tillation the fruit yielded 3.7 per cent, of a leiiion-yellow oil with a 
pecuHar odor, reminding of oil of water-fennel. Continued dis- 
tillation yielded, in addition, 0.9 per cent, of a crystalline substance. 
We were compelled to abandon the attempt to dissolve this sub- 
stance in the oil in the proportion indicated, because the bulk of the 
solid constituents again separated out even at a temperature of 25 
to 30°. The properties of the oil and of the solid substance were 
therefore determined separately. The oil behaved as follows : 

djgo 0.8653, a^ — 23° 35'>n^2o° i.48i3i» acid no. 9.9, ester no. 10.3, 
ester no. after acetyl. 33.6, soluble in 2.6 vol. and more of 90 per cent, 
alcohol. According to these analytical values the oil appears to 
consist chiefly of hydrocarbons, the nature of which remains to be 
elucidated by further investigation. The odor suggests the presence 
of phellandrene. 

The solid substance which was obtained in the process of distilla- 
tion, after being twice recrystallized from alcohol, presented color- 
less, odorless, optically inactive needles or leaflets, m. p. 83°. It 
was readily soluble in ether, chloroform, and acetone, a little less 
readily in alcohol, benzene, and light petroleum (all three of which 
solvents are very suitable for recrystallizing the body), and was 
insoluble in water. The substance is not an acid ; it appears rather to 
be a phenol or lactone-like compound, as is evident from the fact 
that it does not react with solutions of alkahne carbonates, while it 
does react with those of caustic alkalies, from which latter it is again 
separated out by acidulation. Although when heated with benzoyl 
chloride it reacted violently, the yield of the resulting benzoyl com- 
pound was only slight, the greater part of the compound having 
remained intact. After repeated recrystallization from alcohol the 
benzoyl compound formed stout crystals, melting at 89°. 

Dr. A. J. Ultee, of Salatiga, Java, has recently sent us a 
sample of an essential oil which we desire to describe here only 
briefly, as a detailed publication concerning its composition has 
been promised by Dr. Ultee himself. 

Oil of Alpinia Galanga Willd. (Fam. Zingiberacese). This 
oil was of a lemon-yellow color and possessed a peculiar, strongly 
aromatic odor. Its constants were as follows: di5o 0.9847, a^-\- 
4° 20', nj^2o° 1-51638, acid no. 1.8, ester no. 145.6, soluble in its own 
vol. of 80 per cent, alcohol, opalescence ensuing upon the addition 
of 3 vols. According to Dr. Ultee, the oil contains pinene, cineol, 
camphor, and methyl cinnamate. The ester number of the oil indi- 
cates the presence of 42 per cent, methyl cinnamate. 



THE AMEEICAN 

JOURNAL OF PHARMACY 



FEBRUARY, igii 

•* * 

CHEMICAL EXAMINATION OF THE ROOT OF 
LASIOSIPHON MEISSNERIANUS. 

By Harold Rogerson. 

A Contribution from the Wellcome Chemical Research Laboratories, 

London. 

The genus Lasiosiphon belongs to the natural order of Thyme- 
Iceacece, which, although containing about 300 species, appears to 
afford but one drug that has received the official recognition of any 
of the national pharmacopoeias, this being the mezereon bark, from 
Daphne Mezereum, Linne, and other European species of Daphne. 

The plants of the above-mentioned natural order are mostly 
shrubs, a few of which are found in temperate regions of the North- 
ern Hemisphere, but which are more common within the tropics, 
and occur most abundantly in South Africa and Australia. They 
are remarkable, among- other characters, for the great tenacity of 
the inner bark, and, in many species, the latter possesses extremely 
acrid properties. 

In a " Revised List of the Flora of Natal," compiled by J. Medley 
Wood, and published in the Transactions of the South African Philo- 
sophical Society, 1908, vol. xviii, Part 2, p. 218, twenty species of 
Lasiosiphon are enumerated, of which, however, several are un- 
named, and only their approximation to other recognized species 
is indicated. In the list referred to, the following is recorded re- 
specting the plant under present consideration : 

" L. M eisnerianus , Endl,, Var. Inanda, 1800 feet alt.. Wood, 36; 
Van Reenen, 5-6000 feet alt., Wood, 4520; var, near Durban, Wood, 

(49) 



50 Lasiosiphon Meissncrianus. {^FehnZ'y^mT' 

1028; var., Gcrrard and McKoi, 807; near Durban, Wood, 104, 
529; without precise locality, Krauss, 237. Compare also De Can- 
dolle's Prodromus, vol. xiv, p. 594, where the specific name of the 
plant is evidently more correctly written Meissneriamis. 

In a work by Andrew Smith, entitled " A Contribution to South 
African Materia Medica," third edition, 1905, there are several refer- 
ences (pp. 35, 77, 125) to the plant designated by him as Lasiosiphon 
Meisneri — Kaffir, isi-Dikili, from which the following items of in- 
formation respecting its characters and uses may be noted. 

" The Lasiosiphons form a rather notable group. They have a 
heath-like appearance, with a tubular corolloid calyx, limb 5-parted. 
The flowers form a head with an involucre. The roots are very 
stringy and are used as sinnet. They are very scorching-, if chewed, 
and will burn the tonsils and throat for twenty-four hours. Three 
species are used medicinally — L. Meisneri; L. anthylloides ; and L. 
linifolius. The first of these is distinguished by its safifron or dark- 
orange flowers. Its leaves are three-quarters of an inch long, 
and less than one-eighth inch wide, hairy at the back. The in- 
volucral leaves are one-half inch long. 

Lasiosiphon Meisneri is a considerable bush. It is tound in the 
lower basin of the Kat River, near its entrance into the Fish River, 
and is also found in various parts of Tembuland, being there used as 
a cure for snake-bite. The dose is from one-half to three-quarters 
of an ounce of the dried root, but some employ both leaves and 
root. The preparation is by infusion. 

It is somewhat difficult to say what its action in snake-bite 
precisely is, whether it is simply a powerful stimulant, almost blister- 
ing in its action, and long continued, and whether the same property 
does not explain the other uses of the plant. If a small fragment is 
chewed, it is nearly tasteless at first, but its burning quality is pres- 
ently developed. Great caution must be used as to the quantity 
administered. 

" L. Meisneri is also employed in cases of karroo fever, and a 
paste of the leaves for sores." 

It has, furthermore, been noted by Smith {loc. cit., p. 78) that 
" the root should always be used tolerably fresh, as it loses its virtue 
by long keeping." 

One species of Lasiosiphon, namely, L. eriocephahis, Dene., has 
been described in the " Pharmacographia Indica," vol. iii, p. 225. 
This is a native of the Deccan Peninsula and Cevlon, and is common 



Am. Jour. Pharm. ) 
February, 1911. / 



L asiosip hon M eiss neriai iits. 



51 



on the hills of Western India. The plant is a shrub, with leaves like 
the willow, and the bark is a powerful vesicant, this property being 
attributed to a resinous constituent. 

The most recent notice of the Lasiosiphons appears to be that 
contained in a short paper on South African Plants which was con- 
tributed by Mr. G. E. Oliver to the Chemist and Druggist, London, 
April 25, 1908, p. 645. It is there stated that these plants are much 
esteemed among the natives for their tonic and blood-purifying prop- 
erties, and also in the treatment of certain kinds of sore throat. The 
activity of the plant is said to reside chiefly in the root-bark, and 
with regard to the constituents of the latter Mr. Oliver has recorded 
the following observations : " A chemical examination of the root- 
bark shows it to contain a very small quantity of volatile oil, tannin 
(to which its virtue in sore throat would perhaps be attributable), 
and a resin, and it is apparently to this resin that its scorching prop- 
erties are due, as it produces the sensation above referred to on the 
tongue, though it does not yield it to acidulated water when boiled 
with the latter. It contains no alkaloid." 

EXPERIMENTAL. 

The material used for this investigation consisted of the roots of 
the above-described plant, Lasiosiphon Mcissncrianus, Endl., which 
had been kindly supplied by Mr. G. E. Oliver, of East London, Cape 
Colony, and was specially collected for the purpose. 

The roots in question were more or less contorted and very 
irregular in size, some of the larger ones being as much as lo centi- 
metres (about 4 inches) in circumference. They were of a dark 
brown color, very rough and warty on the outer surface, and had a 
relatively thin bark, surrounding a lighter colored, very fibrous 
wood. As has previously been observed, when a little of the bark 
is chewed, a burning sensation is soon developed in the throat, which 
persists for several hours. 

As a prehminary experiment, a small portion (lo grammes) of 
the ground material was tested for the presence of an alkaloid, but 
with a perfectly negative result. 

Another portion (25 grammes) of the ground material was suc- 
cessively extracted in a Soxhlet apparatus with various solvents, 
when the following amounts of extracts, dried in a water-oven, were 
o1)tained : 



52 



Lasiosiphon Meissneriamis. 



f Am. Jour. Pbann. 

I Fcbriiaiy, 1911. 



Petroleum (b. p. 35-50°) extracted. 0.20 Gm. = 0.80 per cent. 
Ether " 0.45 " = 1.80 " 

Chloroform " o.io " =0.40 " " 

Ethyl acetate " 0.60 " = 2.40 " " 

Alcohol " 2.10 " =8.40 " " 



Total, 3.45 Gm. = 13.80 per cent. 



For the purpose of a complete examination a quantity (29.94 
kilogrammes) of the ground material was extracted by continuous 
percolation with hot alcohol, this operation having been kindly con- 
ducted by Messrs. Stafford Allen and Sons, of London. After the 
removal of the greater portion of the alcohol, a viscid, dark colored 
extract was obtained, amounting to 7.98 kilogrammes. 

The whole of the above-mentioned extract was mixed with 
water, and distilled in a current of steam in a suitable apparatus 
for several hours, but no essential oil or other volatile product was 
obtained. 

After the above operation there remained in the distillation ap- 
paratus a quantity of a dark brown resin and a dark colored aqueous 
liquid. The resin was separated by filtration, and well washed with 
hot water until nothing further appeared to be removed. The 
aqueous liquid and washings, on cooling, deposited a brown, resinous 
product, which was separately collected, and amounted to 320 
grammes. A small portion (25 grammes) of this product was 
dissolved in alcohol, mixed with purified sawdust, and extracted in 
a Soxhlet apparatus with the following result : 

Petroleum (b. p. 35-50°) extracted, nil 

Ether 2.0 Gm. ~ 8.0 per cent. 

Chloroform " nil 

Ethyl acetate " 5.0 Gm. = 20.0 per cent. 

Alcohol " 17.0 Gm. = 68.0 per cent. 



Total, 24.0 Gm. = 96.0 per cent. 



These extracts were entirely resinous, and, although subjected 
to treatment both with acids and alkalis, nothing definite could be 
obtained from them. 

The aqueous liquid, from which the resinous material had been 
completely removed, was concentrated to a small bulk, and shaken 
with ether, but only a trace of an amorphous product was thus ob- 



Am. Joor. Fharm. ) 

February, 1911. J 



Lasiosiphon Meissnerianus. 



53 



tained. On subsequently shaking the Hquid with amyl alcohol a 
quantity of amorphous material was removed. • This was heated 
with a 10 per cent, solution of sodium hydroxide, the alkaline liquid 
being then acidified and extracted with ether, but it yielded nothing 
definite. 

The aqueous liquid was then treated with a slight excess of a 
solution of basic lead acetate, when an abundant brown precipitate 
was produced. This was collected, well washed with water, then 
suspended in water, and decomposed with hydrogen sulphide. On 
filtering the mixture, and concentrating the filtrate, a resinous prod- 
uct was obtained which responded to the usual tests for tannic 
matter. 

The filtrate from the basic lead acetate precipitate was treated 
with hydrogen sulphide for the removal of the lead, and the clear, 
filtered liquid evaporated to a small volume. It was found to contain 
a quantity of sugar, since it readily reduced Fehling's solution, and 
yielded J-phenylglucosazone, melting at 204-205°. 

Examination of the Resin. 

The resin which had been separated from the aqueous liquid, and 
thoroughly washed with hot water, as above described, amounted to 
3685 grammes, thus corresponding to 12.3 per cent, of the weight of 
the drug. It was a brown, powdery substance, which, when inhaled, 
had an irritating efifect on the nostrils, and when brought on the 
tongue, especially in alcoholic solution, a burning sensation was soon 
developed, similar to that produced on chewing the bark of the root. 

For the examination of this resin a quantity (300 grammes) of 
it was dissolved in alcohol, mixed with purified sawdust, and the 
thoroughly dried mixture then successively extracted in a Soxhlet 
apparatus with light petroleum (b. p. 35-50°), ether, chloroform, 
ethyl acetate, and alcohol. 

Petroleum Extract of the Resin. 

This was a dark green, amorphous mass, amounting to 26 
grammes. It was dissolved in alcohol, and heated for about four 
hours in a reflux apparatus with an alcoholic solution of potassium 
hydroxide. The alcohol was then removed, water added, and the 
alkaline mixture extracted with ether. The ethereal liquid was 
washed, dried, and evaporated, when a small amount of a crystalline 



54 



L asiosip lion Mc iss iicrianus. 



{Am. Jour. Pharm. 
Felauary, 1911. 



substance was obtained, which separated from alcohol in plates, and 
gave the color reaction of the phytosterols. On recrystallizing the 
substance from a mixture of ethyl acetate and dilute alcohol it was 
obtained in the form of flat needles, melting at 132-133°. 

0.1188, when dried at 110°, lost 0.0056 H.O. H,0 = 4.7 

0.1 132 of anli3'droiis substance gave 0.3468 CO2 and 0.1250 H2O. 

C = 83.5 ;H= 12.2 
, Cj7H4(;0,H20 requires HuO = 4.5 per cent. 

CiiTHinO requires € = 83.9; H 11. 9 per cent. 

This substance is thus seen to be a phytosterol, and a determina- 
tion of its optical rotatory power gave the following result : 

0.2722 of anhydrous substance, made up to 25 c.c. with chloroform, gave 
a£) — 0° 40' in a 2 dcm. tube, whence — 30.6°. 

The acetyl derivative, when crystallized from acetic anhydride, 
separated in needles melting at 110°. 

The alkaline liquid from which the above-described phytosterol 
had been extracted by means of ether was acidified and again ex- 
tracted with ether, the ethereal liquid being dried and the solvent 
removed. A quantity of fatty acids in the form of a dark green mass 
was thus obtained. These acids were distilled under diminished 
pressure, and, by means of their lead salts, were separated into solid 
and liquid portions. The amount of solid acid obtained was 3 
grammes. It distilled between 220 and 230° and, when re- 
crystallized from ethyl acetate, melted at 64°. 

0.1320 gave 0.3634 CO2 and 0.1470 H,0. C = 75.1 ; H = 12.4 
Ci.iHs^Oo requires C = 75.o; H = 12.5 per cent. 

The solid acid thus appeared to consist of nearly pure palmitic 
acid. 

The liquid acids distilled between 215 and 22^°/^-^^. and 
amounted to 2.5 grammes. Determinations of the iodine and neu- 
tralization values gave the following results : 

0.2276 absorl)ed 0.2308 iodine. Iodine value = 101.4 
0.2034 neutralized 0.4025 KOH. Neutralization value =197.9 
Ci.sH.'!402 requires Iodine value = go.o ; Neutralization value = 198.9 

These results indicated that the liquid acids consisted chiefly of 
oleic acid, with a very small amount of an acid of a higher degree of 
unsaturation. 



Am. Jour. Pharin. ) Lasiosipkofi M eissneriauiis. 

February, 1911. J ^ , 



55 



Ether, Chloroform, Ethyl Acetate, and Alcohol Extracts of the Resin. 

These extracts were dark brown, resinous masses, and amounted 
to 24.7, 35.0, 47.0, and 150 grammes respectively. 

The ether and chloroform extracts were examined by shaking 
their respective solutions successively with aqueous sodium car- 
bonate and sodium hydroxide. Furthermore, all the above-men- 
tioned extracts were heated with 5 per cent, sulphuric acid in aqueous 
alcohol, and with a 10 per cent, solution of sodium hydroxide, but 
by none of these methods could any definite product be obtained 
from them. 

Fusion of the Resin with Potassium Hydroxide. 

A quantity (25 grammes) of the powdered resin was gradually 
introduced into 150 grammes of potassium hydroxide in a state of 
fusion, and the temperature of the mixture maintained at about 260° 
for some time. After cooling, the mass was dissolved in water, the 
solution acidified with sulphuric acid, and distilled in a current of 
steam. The distillate contained some volatile acid, which was con- 
verted into a barium salt, the latter amounting to 2.5 grammes. An 
examination of this salt showed the volatile acid to consist chiefly of 
a mixture of formic and butyric acids. 

After the removal of the volatile acids, as above described, the 
liquid in the distillation flask was separated by filtration from a 
quantity of resinous material, and extracted with ether. The ether- 
eal liquid was then shaken successively with a solution of sodium 
carbonate and a 10 per cent, solution of sodium hydroxide. The 
sodium carbonate liquid was acidified and extracted with ether, but 
on evaporating this ethereal liquid only a small amount of a tarry 
residue was obtained, the solution of which gave a green color with 
ferric chloride. The solution of sodium hydroxide removed nothing 
from the ethereal liquid, and on finally evaporating the latter a small 
amount of a dark colored, amorphous product was obtained, which 
possessed an exceedingly unpleasant odor. 

Notwithstanding the very complete examination to which the 
roots of Lasiosiphon Meissnerianus, Endl., have been subjected, it 
will be seen that they have yielded but little of chemical interest. 
The chief constituent of the root is an amorphous resin, to which, as 
had previously been observed, its acrid properties are evidently due. 



56 Preparation of Thyroid Extract. { ^"'.b^uaJy ^m™" 

In conclusion, the author desires to express his indebtedness to 
Dr. F. B. Power for having suggested this research, and for the kind 
assistance he has afforded throughout the course of the work. 



THE PREPARATION OF THYROID EXTRACT FOR 
THERAPEUTIC PURPOSES. 

By S. p. Beebe, Ph.D., M.D. 

During the last ten years there has been a marked increase in the 
interest shown toward the physiology of the internal secretions, 
and the therapeutic value of organ extracts has been the subject 
of much debate. The thyroid gland has been the centre of much 
of this discussion and its usefulness as a therapeutic agent in other 
conditions than those of the classical myxoedema has been demon- 
strated so thoroughly that the demand for a standard preparation 
may no longer be ignored. The manufacturers at the present time 
supply a variety of thyroid products prepared by different methods, 
and undoubtedly of differing therapeutic effects. The terminology 
shows great confusion and the precise nature of the substance that is 
provided is generally not known. For instance, the term iodothyrine 
which was used by Baumann ^ to describe the substance which he 
obtained by hydrolyzing thyroid glands with ten per cent, sulphuric 
acid. This substance was found to make up 2-5 per cent, of the 
glands by weight, it was insoluble in acids, soluble in alcohol and 
alkalies, contained 9.3 per cent, iodine, and from the experiments 
of Roos it was thought .to represent all the physiological activity of 
the gland. The same term, thyreoiodin," was used by Roos ^ to 
indicate " the alcoholic precipitate of a glycerin extract of the well- 
pulverized gland dried at body temperature." In Merck's index for 
1907 iodothyrine is the name given to " milk sugar trituration of the 
active constituent of the thyroid gland, 15 grains of which contain 
1/200 grains of iodine." In some instances supposed thyroid 
preparations have been found to consist of meat proteids impreg- 
nated with potassium iodide, or a poor quality of gland has been 
enriched by the addition of inorganic iodine. 

The experience of clinicians confirms the belief that the commer- 
cial preparations are not uniform and that they are at times entirely 
inactive. Analyses of many preparations now on the market have 



"^F^bSJy.mr"} Preparation of Thyroid Extract. 57 

been made in this laboratory for the iodine content and it has been 
found that the products from various firms differ widely in the con- 
tent of iodine, and also that the same preparations vary from time to 
time. 

The precise relation which iodine has to the physiology of the 
thyroid has been a subject of much discussion and in a recent Bulle- 
tin from the Hygienic Laboratory Hunt and Seidell have reviewed 
the arguments pro and con in regard to this matter, and have given 
the results of a long series of experiments based upon a new method 
to show that there is a very close relation between iodine content 
and physiological activity. The precise function of the gland need 
not be called in question in discussing this point. We know that 
the thyroid gland has a very marked selective absorption for iodine. 
In this laboratory we have made many analyses to determine the 
iodine content of liver, kidney, and muscles taken from animals to 
which large quantities of potassium iodide had recently been given 
and have not found the slightest trace of it, while in the same ani- 
mals the thyroid gland may have had its iodine content increased 
by 200-600 per cent. In vitro there is no more difficulty in iodizing 
a proteid from these other tissues than from the thyroid, so that 
Blum's * belief that proteids artificially iodized in vitro should be 
considered identical to those formed in vivo in the thyroid certainly 
has no justification. 

(Blum has maintained the theory that the function of the thyroid 
is to detoxicate certain metabolic toxins by combining iodine with 
them, and in part bases the theory upon the experimental finding 
that thyroid extract which has been saturated with iodine in vitro 
no longer has the same physiological action that it does before the 
artificial saturation with iodine. From this finding he reasons that 
the addition of iodine destroys the toxic properties of the substances 
brought to the gland in the circulation, and that the more completely 
this is accomplished the less toxic the products are. The fallacy 
of this argument is to be found in the fact that iodizing of a proteid 
in vitro is a drastic chemical process in no way to be compared with 
the physiological action of the thyroid gland.) 

No artificial product has ever been prepared which has the same 
effect upon metabolism, myxoedema, and cretinism that is obtained 
by iodized proteid from the thyroid gland. The discussion of the 
pharmacological action and therapeutic value of thyroid prepara- 
tions need not involve us in discussion of the function of the gland. 



58 



Preparation of Thyroid Extract. 



f Am. Jour. Pbarm. 
( February, 1911, 



DOES THYROID PROTEID FREE FROM IODINE HAVE ANY FUNCTIONAL 

ACTIVITY ? 

This is an old question and it has been the opinion of many 
experimenters from Banmann, Miwa, Stoeltzner, and Neumeister, 
and it has recently been reiterated by John, that because many in- 
stances of iodine-free thyroids were found in animals enjoying 
apparent health, that therefore no essential relation exists between 
iodine content and physiologic action. Hunt ^ has modified this 
opinion somewhat by concluding- that iodine-free thyroid has a mild 
deg-ree of activity, but that it is not to be compared with normal 
iodized thyroid in its protective power to acetonitril poisoning. 

Such a conclusion as well as that of the older investigators is, 
however, open to the criticism that the methods for determining 
the presence of iodine may have been faulty. A large number of 
thyroid glands have been analyzed for iodine in this laboratory dur- 
ing the last three years and we have not found any which were abso- 
lutely iodine free. There is no question that such a finding is due 
to an improvement in the Baumann method of iodine determination. 
According to the Baumann method the thyroid tissue is fused 
in a nickel crucible with sodium hydroxide and sodium nitrate. 
Only sufficient sodium nitrate is used to give a clear fusion mass. 
The melt is dissolved in water, acidified with sulphuric acid, nitrous 
acid added to set free the iodine, which is shaken out with chloro- 
form or carbon bisulphide and estimated colorimetrically. Dr. L. 
W. Riggs,^ working in this laboratory, has shown that during the 
fusion process a variable amount of the iodine is oxidized to iodate, 
which is not subsequently reduced by the nitrous acid, and which, 
therefore, is lost in the extraction with carbon tetrachloride and gives 
too low a reading. 

5 Nal + NalO, + 3H, SO, — > 3L + 3Na, So, -f 3H2O 

According to the above reaction five molecules of iodide set free 
the iodine from one molecule of iodate, and it follows that where 
the proportion of iodate is greater than this some of it must remain 
undetermined. When small quantities of iodine are present in the 
fusion mass a relatively larger proportion of the iodine is oxidized 
to iodate and the proportion of one molecule of iodate to five of 
iodide is exceeded, with a consequence that iodine is lost. When only 
very small quantities of iodine are present it may be entirely oxi- 
dized, and a report given of no iodine found in the gland. The 



Xirar>,mr-} Preparation of Thyroid Extract. 59 

improvement which Dr. Rig'gs has introduced is the addition of an 
active reduction by Devarda's alloy of the solution of the fusion 
mass, thus reducing the iodate to iodide and insuring a full yield. 
The figures given in his paper show that it is with the glands con- 
taining only a very small quantity of iodine that the largest errors 
are made. For instance, with sheep thyroids, which contained only 
.03 mg. iodine per gramme of fresh gland, 77 per cent, of the iodine 
was found after reduction. Subsequent experience has borne out 
these findings and we have repeatedly had glands for analysis which 
were found to be iodine free by the older method, but were found to 
contain marked quantities of iodine after reduction. In no instance 
have we found a thyroid gland free from iodine, and we have 
analyzed a wide variety of thyroid glands during the last two years. 
In view of these facts I am of the opinion that we are not at present 
justified in saying that iodine-free thyroid has an effect similar to 
that obtained by the normal iodized product, and, furthermore, it 
seems probable that many of the results ascribed to iodine-free thy- 
roid are really caused by a proteid containing only an exceedingly 
small quantity of iodine. The recent paper of Hunt and Seidell ^ 
gives the most striking evidence yet published that iodine-free 
thyroid does have the characteristic metabolic effect of the iodized 
gland, but I believe the explanation of their results is to be 
found in the fact that their method of determining iodine was faulty, 
and the cjuantity of material used for iodine analysis too small. 

These authors are agreed, however, that iodine-containing thy- 
roid is much more effective than iodine-free thyroid, and give 
figures to show that the physiological effect is in direct proportion 
to the iodine content. Such a conclusion is in harmony with the 
findings of most students of this subject and agrees with the experi- 
ments made in my laboratory. I regard it, therefore, as probable 
that functional activity is proportional to iodine content, other fac- 
tors being the same. 

The thyroid gland contains a variety of protein substances which 
contain iodine and according to some investigators other iodine- 
free proteids. The methods of isolating these proteins have not 
been uniform and as a result it seems prol^able that authors have 
given different names to the same substances. The most conclusive 
work upon the chemistry of the thyroid has been done by Oswald,' 
who is led to conclude that thyreoglobulin is the characteristic iodine- 
containing proteid found in the gland. He describes another pro- 



6o 



Preparation of Thyroid Extract. 



{Am. Jour. Pharm. 
February, 1911. 



teid, which he names nucleoproteid, free from iodine and without 
functional activity. In my laboratory we have used various methods 
of fractioning the extracts from different types and species of thy- 
roid gland in the hope of obtaining a series of proteids varying 
somewhat in composition and physiological activity. Such a series 
we have obtained, but, contrary to Oswald, in no case have we 
found nucleoproteid or other proteid free from iodine nor have we 
found any of the primary or secondary albumoses obtained on diges- 
tion to be free from iodine. When tryptic digestion, or acid hydro- 
lysis is carried beyond the biuret stage a variety of fragments con- 
taining iodine are obtained. Even in extracts from perfectly fresh 
glands the filtrates obtained after removing the heat coagulable 
proteids contain iodized peptones, and if the glands are not fresh 
the amount of these peptone-like substances is much increased. 

It is evident, then, that when the whole thyroid gland is ground, 
dried, and pulverized for therapeutic use that a variety of iodine- 
containing proteid and non-proteid substances is included. Are 
they all necessary or equally valuable physiologically, and may it not 
be that some of them are actually jiarmful? In an endeavor to 
answer these questions and also to determine the best method of 
preparing the physiologically active portions for therapeutic use 
we have made many experiments. I shall not describe in detail the 
many methods employed to fractionate the proteids, but will outline 
the procedure which we have finally hit upon as the simplest and 
most effective for preparing thyroid extract for therapeutic use. We 
have used glands from sheep, beef, and pig. In so far as we can 
judge by the gross appearance only normal glands are selected and 
this I think is a valuable point, as heretofore only sheep glands have 
been used therapeutically and it became evident very early in this 
work that sheep from certain regions always had goitrous glands 
poor in iodine. Moreover, it was these glands that the abattoir 
preferred to furnish since they were sold by the pound and the 
glands necessary for a pound were more easily obtained if goitres 
were used. I have seen such glands in the course of preparation 
into thyroid extract at two commercial laboratories. Such glands 
are rich in proteid of the thyreoglobulin type but very poor in iodine. 
Obviously here is an adequate source for much of the variation of 
thyroid preparations. The normal glands are obtained in as fresh 
a condition as possible and are kept from autolysis by freezing. 
They are ground to a fine pulp and extracted with three to four 



^?;birarV,79i™'} Preparation of Thyroid Extract. 6i 

times their volume of normal saline solution made very faintly alka- 
line by sodium hydroxide. Three or four drops of a ten per cent, 
solution of sodium hydroxide are added to every litre of salt solu- 
tion. The extract is shaken vigorously at room temperature for one 
or two hours and is then transferred to the refrigerator, where it 
is allowed to remain for twelve to eighteen hours. At the end of 
this time a large portion of the proteid has been dissolved by the 
saline. The clear extract is obtained by filtering first through gauze 
to remove the larger fragments and then through paper pulp by the 
help of a Buchner funnel, after the method of Osborne. As stated 
before, this extract contains a variety of proteids and proteid frag- 
ments and our object is to separate the pure iodine containing glob- 
ulin from the other constituents by as brief and simple a method 
as possible. This may be accomplished by salting out the proteid, 
filtering and finally dialyzing the precipitate, a procedure which re- 
quires a great deal of time and which exposes the product to abun- 
dant opportunities for infection and decomposition. The plan we 
have finally adopted is to acidify with acetic acid and heat to 44° C. 
for 10 minutes. Extracts of the different species of glands behave 
in characteristic fashion. The addition of acetic acid to extract of 
sheep glands gives a scanty precipitate or none at all ; such as does 
form may be filtered out and is found to be richer in iodine than any 
fraction obtained subsequently. On heating an abundant flocculent 
precipitate is obtained at 44° C. This precipitate is rich in iodine, it 
dissolves readily in a weak alkaline solution, and is precipitated again 
by acetic acid. Its behavior with regard to dialysis and salt pre- 
cipitation is that of a globulin ; it contains more iodine than any 
proteid obtained from the filtrate heating to a higher temperature, 
and is by far the most abundant proteid in the gland. If this pro- 
teid is removed by filtration and the filtrate heated to a higher tem- 
perature, a further precipitate is obtained at 65 ^-70°, a third at 
82°-86°, and a fourth after boiling for some time. All of these pro- 
teids contain iodine but in relatively much less amount than in the 
precipitate at 44°, they form only a small part of the entire proteid 
content, and they do not redissolve in a weak alkaline solution. 

After all coagulable proteids are removed the filtrate contains 
substances giving the proteid color reactions and containing a by 
no means negligible quantity of iodine. If the whole gland extract 
is used for therapeutic purposes it follows that all of the various 
iodized fractions are administered. I believe that some of these sub- 



62 



Preparation of Thyroid Extract. 



( Am. Jour. Pharm. 
( February, 1911. 



Stances not only give no beneficial therapeutic action but are actually 
harmful. 

The following experimental evidence is offered in partial substan- 
tiation of this statement. Four lots of guinea pigs were given 
identical amounts of iodine, .0001 mgm. of iodine for each 100 
grammes body-weight. The first lot in the form of purified thyreo- 
globulin, precipitated from the protein extract by acidifying with 
acetic acid and heating to 44° C. The second lot in the form of the 
alcohol-soluble portion of the filtrate from the pepsin digestion of 
the glands. The third lot in the form of the alcohol-soluble portion 
of the residue from the pepsin digestion of the gland. The fourth 
lot from the alcohol-soluble portion from extracts from normal 
glands after removing all the coagulable proteid. The second and 
fourth fractions give all the proteid color reaction, but compared 
with the nitrogen content they contain relatively much less iodine. 
The third fraction corresponds to iodothyrin, and as will be seen 
it is very rich in iodine. To be certain of the dose which each ani- 
mal received, the administration was by hypodermatic injection in 
each instance. The relation of iodine to nitrogen in each of these 
substances was as follows : 

1. Sheep thyreoglobulin. 

I c.c. solution contains 1.25 mgm. nitrogen. 

I c.c. contains 0.012 mgm. iodine. 

I gramme nitrogen contains .0096 gramme iodine. 

2. Pepsin digestion filtrate, alcohol-soluble portion. 
I c.c. contains 7 mgm. nitrogen. 

I c.c. contains .0375 mgm. iodine. 

I gramme nitrogen contains .00535 gramme iodine. 

3. Pepsin digestion residue, alcohol-soluble portion. 
I c.c. contains 0.14 mgm. nitrogen. 

I c.c. contains .09 mgm. nitrogen. 

I gramme nitrogen contains .6428 iodine. 

4. Alcohol-soluble portion of extracts from sheep glands 

after removing all coagulable proteid. 
I c.c. contains 10.22 mgm. nitrogen. 
I c.c. contains .044 mgm. iodine. 
I gramme nitrogen contains .0043 gramme iodine. 
The pigs receiving iodine in the form of the thyreoglobulin 
increased fifty per cent, in weight during the experimental period, 
which lasted nearly two months, and had no pathological disturbance 



"^Sbiuatx^m^^^^ Preparation of Thyroid Extract. 63 



whatsoever from the injections. They were scarcely to be deter- 
mined from the control pigs that received no injections whatsoever. 
The pigs receiving the alcohol-soluble portion of the filtrate from 
pepsin digestion lost weight, and all three died during the first 
month with a large loss of weight. The pigs receiving the alcohol- 
soluble portion of the pepsin digestion residue, corresponding to 
iodothyrine, increased in weight like the normal animals and were 
not to be distinguished from the animals receiving the proteid injec- 
tions. Those animals receiving the alcohol-soluble portion of the 
extract from the sheep glands from which all coagulable proteid had 
been removed gained somewhat in weight, but one died in convul- 
sions before the experimental period was over, while the other two 
were not to be compared with the control pigs. From these results 
we must conclude that the second and fourth fractions were toxic. 
Their precise nature we do not know, but the behavior is that of a 
simple peptone. Somewhat similar results have been obtained from 
other of the cleavage products, and further experiments have given 
us conclusive evidence that these substances are, in proportion to 
their iodine content, not to be compared with the thyreoglobulin in 
protecting mice from acetonitril poisoning. The extensive experi- 
ments of Cunningham ^ give facts which coincide with the results 
obtained in this laboratory : z'/,c'., the autolyzed thyroid gland con- 
tains toxic substances. 

Since the discovery of iodothyrine, it has been generally con- 
sidered that this substance is the physiologically active principle of 
the thyroid gland, and that all the effects upon metabolism peculiar 
to thyroid activity could be duplicated by the administration of this 
substance by mouth. It is the writer's opinion that such a conclusion 
is not justified by the facts. 

The physiologically active substance in the thyroid is elaborated 
by the active cells lining the alveoli, and it seems probable that under 
normal conditions a considerable amount of this substance is secreted 
into the alveoli and retained there as reserve material. It may, 
however, pass from the gland cell directly into the blood and in some 
pathological conditions we find practically no colloid, but an un- 
usually well vascularized, actively proliferating parenchyma, asso- 
ciated with symptoms of over-activity of this gland. As we find the 
secretion in normal glands it is not in the form of iodothyrine, but 
in the form of an iodized proteid, and a drastic chemical process is 
required to li1)crate the iodotliyrine. Furtliermorc, the secretion 



64 Preparation of Thyroid Extract. {^^^bfSal^'y^rjT™' 

enters the blood directly and not through the stomach. To imitate 
the physiological conditions I am convinced that we should adminis- 
ter the same biological sort of thyroid proteid by hypodermic injec- 
tion. The human patient should receive human thyroid proteid 
by hypodermic injection. Of course such a conclusion is of theoreti- 
cal interest only, but during the last three years I have had many 
opportunities to compare upon human subjects the effects produced 
by administration of various forms of thyroid preparations and from 
these observations the only possible conclusion is that the human 
thyroid is by far the best for the human subject. When we give 
the human thyroid extract we give a substance ready for instant use, 
and a comparatively small quantity will act more effectively from 
the qualitative and quantitative stand-point than a larger quantity of 
any other kind of thyroid material. These other forms probably 
act very largely by stimulating the gland of the individual to whom 
they are administered. 

In its effects upon simple goitre, myxoedema, cretinism, athyroid 
symptoms found occasionally in the later periods of exophthalmic 
goitre, and various metabolic disorders associated with hypofunc- 
tion of the thyroid, there is no other substance which acts so eco- 
nomically and efficiently as the proteid precipitated from extracts 
of normal human thyroid glands by acetic acid and heat to 44° C. 

For the reasons above outlined we should use only the proteid 
obtained by a similar method from animal glands. Accordingly the 
original precipitate is washed repeatedly with normal saline by de- 
cantion or centrifugation until the wash-water is free from biuret 
reacting substances. It is then dissolved by the addition of a little 
sodium hydroxide, the solution filtered through a thick paper mat and 
again precipitated by acidifying with acetic acid. Heat is rarely 
required for the second precipitation. The washing process is re- 
peated and more proteid-like material removed from the precipitated 
globuhn. The final washed precipitate is centrifugated or filtered 
out and dried at low temperature, or it may be kept in solution and 
after filtration through a Berkefeld kept for hypodermic adminis- 
tration. 

Proteids have been prepared in this manner from glands of pigs, 
beeves, sheep, and the human gland. The prepared proteid shows 
quite as wide a variation in its iodine content as do the fresh glands. 
In the following table is given a series of iodine analyses of thyroid 
glands obtained from healthy animals. 



""^^b^aryfmr"} Preparation of Thyroid Extract. 65 



Iodine in Milligrammes Per Gramme of Fresh Gland from Different 

Species. 



Pig. 


Sheep. 


Beef. 


Human. 


.084 


.006 


.030 


.060 


.120 


.013 


.040 


.080 


.300 


.016 


.103 


.094 


.300 


.016 


.165 


.200 


.648 


.018 


.168 


.216 


.710 


.018 


.187 


.316 


1.040 


.020 


.260 


•415 


1.340 


.041 


•445 


.615 


1.470 


.214 


.610 


.814 


2.050 


.318 


.700 




2.88 


415 


1.020 
1.470 





From the above table it is evident that the iodine-content of thy- 
roid glands shows wide variations. Before being used therapeutically 
it is essential that the proteid should be standardized on the basis of 
its iodine content, and a uniform intelligent dosage regulated thereby. 
For the standard we have selected the proteid obtained from normal 
human thyroid glands. 

The average figures of a large number of iodine analyses of the 
proteid obtained from normal human thyroid glands by the process 
above described, namely, that of heating the acidified extract to 44° 
and thoroughly washing the precipitate, is as follows : 



ONE GRAMME OF THE PURIFIED PROTEID FROM NORMAL HUMAN THY- 
ROID GLANDS CONTAINS 3.384 MILLIGRAMMES OF IODINE. 

After the purified proteid from the animal glands is obtained, 
its iodine content is determined after the method devised by Dr. 
Riggs, noted above, and regardless of whether this proteid is richer 
or poorer in iodine than the standard, it is considered that each 
3.384 mgms. of iodine represent one gramme of the active thyroid 
proteid. For the purpose of therapeutic administration the proteid 
is diluted with the appropriate amount of lactose and made up into 
two-grain tablets by the usual method. Tablets of different strengths 
are prepared ; i per cent., 2 per cent., and 5 per cent, tablets have 
been found to give a sufficiently wide variation in strength to answer 



66 



Preparation of Thyroid Extract. 



j Am. Jour. Pharm. 
I JMl.iuary, 1911. 



all the usual requirements. By i per cent, tablet is meant that i 
per cent, of the dried weight of the tablet is made up of the purified 
thyroid proteid according to the standard above described. This 
may seem to be a very small dose, but our experience proves to us 
that many patients cannot take a stronger tablet than this. The 
I and 2 per cent, tablets are used almost entirely in the treatment of 
various types of goitre, some of them being of the atypical exoph- 
thalmic variety. It is well known that these patients cannot stand 
heavy dosing with thyroid proteid. The stronger 5 per cent, tablets 
are reserved almost exclusively for different metabolic disorders, 
such as various skin lesions or joint conditions, myxoedema, cretin- 
ism, or those conditions in which there is a markedly deficient thyroid 
activity. It will be observed that by the method of standardizing 
and preparing the proteids for therapeutic administration, a uniform 
physiological activity may be expected, regardless of the character 
of the glands from which the proteid was obtained. A 5 per cent, 
tablet always contains the same cjuantity of iodine whether the 
proteid from which it was made comes from a pig gland containing 
a relatively high quantity of iodine or from a sheep gland contain- 
ing a relatively low quantity of iodine. For some purposes it has 
been found advisable to administer the proteid hypodermatically 
and, accordingly, solutions of the proteid in varying strengths, stand- 
ardized on the iodine basis, have been put up in sealed glass tubes. 
The products prepared according to the method here outlined have 
been in use for about two and a half years. They have been em- 
ployed in a wide variety of clinical conditions by a considerable num- 
ber of experienced clinicians, and the results have demonstrated 
their value to such an extent that I have no hesitation in saying that 
this method of preparing and standardizing thyroid is superior to 
any method now in vogue, that it gives all of the physiologically 
active portions of the gland, that it contains none of the toxic, dele- 
terious substances contained in the whole extract. In my judgment 
there is no reason for supplying the wide variety of thyroid prepara- 
tions which now appear upon the market. The methods described 
above give everything that is necessary in such form that every 
therapeutic need is satisfied. 

REFERENCES. 

^Zeit. Physiol. Chem., vol. 21, p. 321, 1896. 
- Zcit. Physiol. Chem., vol. 21, p. 23, 1896. 



Am. Jour. Pharm. | 
February, 1911. ) 



A nti-Na rcotic L cgislatio n . 



67 



Bulletins of the Hygienic Laboratory, U. S. Public Health and Marine-Hos- 
pital Service, No. 33, 47. 
^ Blum. Miinchener Medisinische W ochenschrift, 1898, No. 9-1 1; Zcit. Physi- 
old. Cheni., vol. 26, p. 160, 1899. 
Zeit. Physiol. Chem., vol. 22, p. 1, 1896. 
'^Journal of American Chemical Society, vol. 31, p. 710, 1909; Ibc'd, vol. 32, 
p. 692, 1910. 

Zeit. Physiol. Chem., 23, p. 265, 27, p. 32; Virchow's Archiv, 169, p. 444, 
1902; Hoffmeister's Beitrage, 11, p. 545, 1902; Wiener klinische Rund- 
schhau, 1905, p. 649. 
^Cunningham: Journal of Experimental Medicine, vol. iii, p. 225, 1898. 



ANTI-NARCOTIC LEGISLATION.- 
By Samuel M. Clement, Jr. 

I consider it a great honor to be invited by the Philadelphia Col- 
lege of Pharmacy to discuss with your professors and your students 
the interesting question of the Law of Narcotics. I have been in- 
tensely interested with this subject for the past year, and I realize 
how important the subject is, not only to pharmacists and physicians, 
but to the entire community ; for, in the time that I have been work- 
ing with the State Pharmaceutical ]>oard and my friend Dr. 
Christopher Koch, I have been amazed at the evils to the community 
resulting from the misuse of narcotics. 

It will be interesting to note that the first legislation enacted on 
the subject of narcotics in the United States was in the Tarifif Bill 
of July 14, 1832, when opium was permitted to be imported to this 
country without duty ; and each succeeding tariif law permitted the 
free entry of opium, until the Tariff Act of August 30, 1842, was 
passed, and for the first time a duty varying from 75 cents to $2.50 
per pound was placed on opium. This continued until October i, 
I890, when the Tariff Law again placed opium on the free list, 
where it remained until July 24, 1897, when the Tariff Law of that 
year placed a duty of $t.oo a pound on opium. It was in 1850 thai 
it was discovered that the Chinese of the I^acific coast were smoking 
large quantities of opium, and a few years after that the lower 
classes of the whites and negroes took to smoking opium ; so that 



* Address delivered before the members of the Philadelphia College of 
Pharmacy, Friday, November tt, 19TO. 



68 



Anti-N arcotic Legislation. 



{ Am. Jour. Pharm 
I February, 1911. 



a Special schedule on opium used for smoking was placed in the 
Tariff Act of July 14, 1862, and put on it a tax of 80 per cent, ad 
valorem. 

It was considered at that time by those interested in discouraging 
the smoking of opium, realizing what a deleterious effect it would 
have on those addicted to its use, that a large duty was advisable, 
believing that it would prevent its importation ; but it soon became 
apparent that the use of the drug was becoming prevalent and that 
the quantities brought into this country did not- diminish, but in- 
creased ; this due to the fact that it was being smuggled into this 
country in very large quantities. 

In the Tariff Act of June 30, 1864, in a special schedule, on opium 
used for smoking a duty of 100 per cent, ad valorem was placed; but 
this cUd not have the desired effect of preventing the importation of 
opium. The Tariff Act of July 14, 1870, placed a rate of $6.00 a 
pound on opium used for smoking, and the Tariff Act of March 3, 
1883, again increased it to $10.00 a pound. On October i, 1890. 
the Tariff Bill made a further increase to $12.00 a pound. It 
seemed, however, that the more duty was placed on opium, the 
smaller were the Custom returns and a larger amount of opium 
smuggled into the country ; so that the tax on opium failed to have 
any effect in diminishing its general use, and the Dingley Tariff 
Bill of July 24, I897, reduced the duty to $6.00 a pound. The next 
general legislation on the subject of opium was the National Food 
and Drugs Act of June 30, 1906, which made it mandatory for 
every one to declare the presence and quantity of opium contained 
in any article, either used as a medicine or used for food, or which 
contained any of the derivatives of opium. On February 9, 1909, 
Congress passed an Act absolutely forbidding the importation of 
smoking opium and making the possession of it a crime punishable 
by imprisonment. The wisdom of this legislation will become 
apparent as we review the general subject further on, because the 
members of Congress at last realized that smoking opium and the 
derivatives of opium are the worst menace to the human race that 
could possibly be imagined. The Tariff Act of 1909 put a duty on 
crude or medicinal opium containing 9 per cent, or over of morphine 
of $1.50 a pound, and under 9 per cent. $6.00 a pound. From i860 
to 1890 the tariff on morphine varied from $i.oo-to $2.50 per ounce, 
and from 1891 to 1897 the duty on morphine was 50 cents an ounce ; 
but, after 1897, it became $1.00 an ounce and in 1909 it became $1.50 



Am. Jour. Pharm. ) 
February, 1911. j 



Anti-Narcotic Legislation. 



69 



per ounce. Prior to 1898 cocoa leaves and cocaine were admitted 
free of duty, but the alkaloid bore a duty of 25 per cent, ad valorem 
up to 1909. The Tariff Bill of 1909 placed a duty of five cents per 
pound on cocoa leaves and of $1.50 per ounce on cocaine. The 
General Appropriation Bill passed May 27, 1908, fixing the appro- 
priation for the Post Office Department of the United States, con- 
tained the following words : 

" No part of the appropriation herein made shall be used for the 
carrying in the mails of any malt, vinous, or intoxicating liquors, or 
intoxicating liquors of any kind ; or any cocaine or derivative 
thereof." 

It is interesting to note that on February 26, 1909, The American 
Association for the Advancement of Science on National Health 
passed the following resolution : 

" We favor a prohibitory tariff, internal revenue tax, and other 
means which will restrict the use of cocaine, its substitutes and de- 
rivatives, to medical purposes.^' 

The revised penal laws of the United States, which took effect 
January i, 19 10, and which were compiled under the direction of one 
of the Congressmen from our own State, the Hon. R. O. Moon, gave 
the Postmaster-General of the United States the power to prevent 
the passage of cocaine through the mails. 

With these thoughts on the national legislation, let us turn our 
attention to what has been done in the way of legislation on the 
subject of narcotics by the various States. Forty-five States have 
passed legislation prohibiting the sale of cocaine except when sold 
under the prescription of a doctor. Twenty-four of the States regu- 
late the sale of opium and its derivatives, and thirteen restrict the 
sale of chloral. There are three States that have not, as yet, 
passed any legislation on the subject of narcotics. A few States — 
and I am proud to say Pennsylvania is one — make it a crime to have 
cocaine in your possession. 

With this great variance between the laws of the various States 
and the laws of the national government, let us consider for a mo- 
ment in what a chaotic condition is this general subject, so important 
to the welfare of the citizens of our great country. Dr. Hamilton 
Wright, who has been placed by President Taft in a position of 



70 



A nti-Narcofic Lcoislatioii. 



/Am. Jour. Pharm 
\ February, 1911. 



authority in connection with the Department of State for the pur- 
pose of investigating the general subject and reporting to the Presi- 
dent the result of his investigation, has made a very careful study of 
the general subject and he has published from time to time statistics 
that are most interesting and which, I believe, will have the effect 
of arousing a great public sentiment on this question. Dr. Wright 
has made a most thorough investigation, and great credit is due to 
him and the Department of State for what he has already accom- 
plished. We find from Dr. Wright's statistics that, during the 
period from i860 to 1869, there was imported into the United States 
1,425,196 pounds of opium of all forms, and, during the period 
from 1900 to 1909, there was imported 6,435,623 pounds of opium. 
This, you will see, is an increase of 351 per cent, of opium im- 
ported into this country, while the population of the country during 
the same periods shows only an increase of 133 per cent. There 
are in the United States to-day ab.out 120,000 Chinese, 35 per cent, 
of whom smoke about 100,000 pounds every year. As I said a few 
moments ago, it was discovered in i860 that smoking opium had 
been adopted by the lower classes of the whites and negroes of this 
country, and this has grown so that we are told to-day that there 
are about 150,000 Americans who smoke annually about 68,000 
pounds of opium. We frequently find, especially along the Pacific 
coast, white women who are living with Chinamen and smoking 
opium. 

It will be interesting to note, by way of comparison, what effect 
opium has on the other countries. Italy, with a population of about 
33,000,000, imports and uses but 6000 pounds of opium. Austria- 
Hungary, with a population of about 46,000,000, uses between 3000 
and 4000 pounds of opium. Germany, with a population of about 
60,000,000, uses about 17,000 pounds of opium a year, and Holland, 
with a population of about 6,000,000, imports and uses but 3000 
pounds per annum. To the credit of all of these old countries, it 
can be said that they have the strictest laws regulating the sale of 
habit-forming drugs. 

It is appalling when we consider that in the United States with 
a population of about 90,000,000 people, we consume the enormous 
quantity of over 400,000 pounds of opium every year — more than 
all the other countries I have mentioned put together. It has been 
conservatively estimated that only 25 per cent, of this enormous 
amount can find any legitimate use and that the balance of 300,000 



Am. Jour. Phann.f 
February, 1911. ( 



Anti-Narcotic Legislation. 



71 



pounds is used by the fiends, either in the form of smoking or by 
using morphine. It is said that 80 per cent, of the 400,000 pounds 
used in this country is used in the manufacture of morphine and that 
about 75 per cent, of morphine made in the United States is used 
by dope fiends. It will be interesting to know that these dope fiends 
are divided as follows : 

Six per cent, of all the persons entering our large penal institu- 
tions have been found to be addicted to the opium habit in some 
form, and of the general criminal population of this country 45.48 
per cent, are habitues of opium, morphine, or cocaine ; 21.6 per 
cent, of the lewd women of this country and their hangers-on are also 
addicted to the drugs ; 2.06 per cent, of the medical profession of 
this country are addicted to drugs; 1.32 per cent, of the trained 
nurses of this country are addicted to drugs ; .684 per cent, of other 
professions are addicted and .18 per cent, of our adult population, 
outside of those enumerated, are addicted to opium or its derivatives. 

We find that outside of the large cities, even into the country dis- 
tricts, the use of opium and its derivatives has increased tremen- 
dously. One hundred and fifty thousand ounces of cocaine are 
manufactured annually in the United States, of which about 135,000 
ounces go to make demons out of human beings. Cocaine is without 
exception the most dangerous drug known to society. It is seduc- 
tive in character and produces a sense of keen exhilaration and 
exaggerated power. It completely wrecks the individual and makes 
a dangerous criminal of him. A man or woman charged with 
cocaine will commit any crime or stoop to the lowest and most im- 
mortal acts. Most of the crimes committed by the Southern negroes 
are the result of coke-charged brains. It has been found that the 
cocaine habit is becoming very prevalent among the negro race, 
not only the negroes of the South, but the negroes of our own 
city and other cities of the North, and it has been found that in cer- 
tain low dives in the South much of the whiskey sold is doctored 
with cocaine. 

It has been said that the cocaine habit is essentially American ; 
but do not let us think for a moment that it is confined entirely to 
the lower classes. In fact, it has invaded the higher ranks of the 
so-called society of our country, and it is astounding to find how 
general is its use among those who consider themselves the great 
social leaders of the country. Cocaine has invaded even the ranks 
of the Army and the Navy, and I regret to say that it has even 



72 



A nti-Na rcotic L c gisla tion . 



jAm. Jour. Pharm. 
I February, 1911. 



been found in the school-room ; for in our own city we found 
schoolchildren buying cocaine from negroes in five and ten cent 
packages. 

These statements are made with the idea of arousing a sentiment 
on this general subject ; for, if it is not checked, no one can tell to 
what extent the evil is going to affect this country and its people. 

It is known that the drug habit is a sort of a secret habit and 
all people who use drugs do so with the greatest secrecy. The 
best step that can be taken is to eliminate the secrecy as much as 
possible, and I desire to express my appreciation to the newspapers 
of Pennsylvania for having given the general crusade against cocaine 
so much publicity ; for I know of nothing that will help to eliminate 
this terrible habit among our people more than publicity. 

There should be an agreement between nations so that smuggling 
of opium will be impossible ; secondly, we should have a Federal 
law to control the interstate traffic ; and, third, we should have a uni- 
form interstate law ; because, of course, the national government 
can only control interstate commerce, but cannot control interstate 
trade. Next we must have laws that will be far-reaching and will 
carry with them severe punishments, and we must have eternal vigi- 
lance and honest, capable, trustworthy officials to enforce the law. 
At this time I desire to express my great appreciation for the noble 
work done in hunting out the sellers of opium and cocaine by the 
Department of Public Safety of Philadelphia. The Director of that 
Department and his assistants have been untiring in their efforts to 
co-operate with the State Pharmaceutical Board, and the records of 
the Court of Quarter Sessions of Philadelphia County will show 
that a great many of them have been punished and a great many 
more are still to be punished when the cases are tried. 

President Taft has appointed delegates to the International Opium 
Congress, and we believe that an international agreement will be the 
result. 

In framing legislation we should remember that drug fiends are 
largely the victims of circumstances and are more to be pitied than 
censured ; but the careless physician who prescribes cocaine or 
morphine, or the careless pharmacist who refills prescriptions for 
cocaine and morphine, are the ones who should be severely dealt 
with, and the sale of patent and proprietary remedies doped with 
morphine and cocaine should be prohibited and the manufacturers 
should be severely punished, for we find proprietary remedies 



Am. Jour. Pharm. > 
•February, 1911. J 



Anti-Narcotic Legislation. 



73 



recommended, for infants as well as adults, containing morphine 
and cocaine, and many a dope fiend to-day can properly charge the 
forming of that habit to the taking of morphine when a child, in 
patent medicines. 

As I said a moment ago, the Federal government cannot prohibit 
the use of cocaine or morphine in the States ; all it can do is to regu- 
late interstate commerce with respect to it and prohibit importation, 
which will be done. The duty rests upon each individual State, how- 
ever, to pass legislation which will be uniform, so that there will be 
no question of jurisdiction; so that there will be no question of 
one State prohibiting cocaine and another one permitting it. Penn- 
sylvania has taken the lead in the legislation with reference to 
cocaine and morphine, and the officials of Pennsylvania, both State 
and municipal, have demonstrated that this evil can be dealt with 
successfully. 

The following are some of the essential features of Hamilton 
Wright's Interstate Bill : 

First: " That such an Act should demand the registration of every 
person who imports, produces, manufactures, compounds, 
distributes, or otherwise handles habit-forming drugs in in- 
terstate or foreign commerce. 

Second: " That importers, wholesale compounding pharmacists, and 
wholesale dealers should pay a small per-annum tax of $io, 
and that retail pharmacists and other retail dealers, includ- 
ing physicians who buy in interstate commerce and who 
carry large supplies of the drugs, should pay a tax of from 
$1 to $3 per annum ; that every one engaged in handling 
drugs should register and pay a tax." 

Third: " That, without attempting to derive a revenue beyond the 
amount necessary to administer the act, all of the habit- 
forming drugs should have imposed upon them an internal- 
revenue tax of I cent an ounce, and that such tax should be 
paid by affixing to packages or other receptacles containing 
the drugs, an engraved stamp, to be affixed and cancelled 
according to law." 

Fourth: " That all compounds or preparations manufactured from 
the original tax-paid drugs should be marked or branded in 
such a manner as to show the payment of the tax on the 
original drug." 



74 



Anti-Narcotic Legislation. 



(Am. Jour. Phann. 
X February, 1911. 



Fifth: " That every person concerned in the importation, manufac- 
ture, remanufacture or compounding, selhng or dispensing 
of habit-forming drugs and their preparation, should keep 
such books, render such returns, and give such bonds as 
may be determined by the Commissioner of Internal Reve- 
nue, with the approval of the Secretary of the Treasury." 

Sixth: ''That it should be unlawful for any person to sell, give 
away or otherwise dispose of in Interstate Commerce, any 
of the habit-forming drugs, their salts, derivatives, or prep- 
arations to any person other than a person who has regis- 
tered and paid the special tax, public hospitals and scientific 
and public institutions excepted." 

Seventh: " That all of such drugs, their derivatives and preparations 
imported should pay an internal-revenue tax equal to that 
imposed on the home-produced drugs." 

Eighth: " That on trial for violation of such an act, illegal possession 
of such drugs should be deemed as sufficient evidence of 
such violation, unless the defendant shall explain the pos- 
session to the satisfaction of the jury.'' 

Ninth: That all returns required by such an Act should be filed 
and recorded in the office of the Commissioner of Internal 
Revenue, under such regulations as may be approved by 
the Secretary of the Treasury, and that these returns should 
be open to the inspection and certified copies should be made 
to the proper officials of any State, territory, or district 
under the jurisdiction of the United States who are charged 
with the enforcement of local laws regulating the prescrib- 
ing, dispensing, sale, or use of such drugs." 

Tenth: ''That heavy penalties, either by fine or imprisonment, or 
both, should be imposed on the violator of such an Act." 

By making this a revenue measure, it is placed in charge of the 
Treasury Department and that Department has a well-trained corps 
of collectors and secret service men, who could see to the proper 
enforcement of the Act. 

I should like at this time to read to you a few thoughts with 
reference to legislation in the State of Pennsylvania that it would 
be well for you to consider, and T am also delighted to say to you 
that Senator James P. McNichol has promised me that he will 
father the legislation in the next House and Senate for the regulation 



X^ry,mr-} Anti-Narcotic Legislation, 75 

and sale of cocaine and morphine and will insist upon the severest 
penalties being placed in the Act, so that all those that we have 
been discussing who violate the law can be properly dealt with. 

The following outline is suggested for a State Anti-Narcotic 
Law : 

Cocaine, Eucaine, and Other Synthetic Substitutes, Their 
Derivatives, Salts, and Compounds. 

1. Sold only on prescription of a registered physician, a dentist, 
or a veterinarian, which is not to be renewed or copied and must be 
kept on a separate file for five years, and a veterinarian shall not 
prescribe for human beings. 

2. Wholesale druggists can sell to retail druggists, other whole- 
sale druggist, or manufacturer of same article. 

3. Manufacturers can sell to other manufacturers of same article 
or to wholesale druggists. 

4. Manufacturers, wholesale druggists, and retail druggists shall 
keep accurate records of all sales and use of all cocaine, etc. 

5. Manufacturers, wholesale druggists and retail druggists shall 
make monthly reports to the body or commission entrusted with the 
enforcement of the law, showing all sales and other uses to which 
it has been put. 

6. Illegal possession a crime. 

7. Prescription files and records subject to inspection of proper 
ofificers. 

8. Severe penalties of imprisonment. 

Morphine, Opium, or Their Derivatives or Compounds. 

1. Sold only on prescription of registered physician, dentist, or 
veterinarian, which is not to be renewed or copied and to be kept on 
a separate file for five years. A veterinarian shall not prescribe for 
human beings. 

2. Wholesale druggists can sell to other wholesale druggists, or 
manufacturers of same article or to a retail druggist. 

3. Manufacturers can sell to other manufacturers of the same 
article, wholesale druggists, or retail druggists. 

4. Manufacturers, wholesale druggists, and retail druggists shall 
keep accurate record of all sales and use of all morphine, opium, 
its salts, derivatives, and compounds. 

5. Manufacturers, wholesale druggists, and retail druggists shall 
make monthly reports to the body or commission entrusted with the 



76 



Anti-N arcotic Legislation. 



i Am. Jour. Pharra. 
( February, 1911. 



enforcement of the law, showing all sales and other uses to which 
it has been put. 

6. A physician may prescribe but not dispense these drugs to 
habitual users under treatment, provided he keeps a record of the 
patient, together with the name and quantity of drug prescribed, 
and reports the same in monthly reports to the body or commission 
enforcing the law. 

/. Illegal possession a crime. 

8. Prescription files and records subject to inspection of proper 
officers. 

9. Severe penalties of imprisonment. 

The Act not to apply to cough remedies, proprietary medicines, 
or other medical preparations sold as medicines and not for the 
purpose of evading the provisions of this Act or supplying habitues 
with the drug if they contain not over (to the ounce) 

2 grains of opium, 
yl grain of morphine, 
34 grain of heroin, 
% grain of codeine. 

(Or not more of any other derivative or compound of same.) 

Providing the quantities of the drugs contained shall be plainly 
stated upon the label. 

Also providing that any preparation intended for soothing syrups 
for infants shall not contain any of the drugs. 

Also providing that regular practising physicians can supply the 
drugs, providing they comply with the other provisions of this Act 
of Assembly with reference to reporting and keeping a record. 

And providing that prescriptions or orders for plasters, liniments, 
and ointments when intended for external use only, and when the 
quantity of the drug is plainly marked on the label, shall be per- 
mitted. 

In conclusion, permit me to say that I believe that if laws such as 
these were passed by the national government, and the different 
States of this Union, there is no reason why the Narcotic Laws of 
the country should not then be effective ; but even with the best of 
legislation, we should always remember that " eternal vigilance is 
the price of liberty and I know of no better means of keeping this 
agitation before the State than through the columns of the news- 



Am. Jour. Pharm. ) 

February, 1911. / 



Abstracts of Papers. 



77 



papers of Pennsylvania. It is true that it may be said that these 
laws will be a little burdensome for the pharmacists ; but they should 
remember that the laws are for the protection of their brother man 
and that they should be willing to bear part of the burden, for if 
the pharmaceutical profession should not be willing to assume its 
share and assist in the passage of some practical law, it is more 
than likely that some others, not accjuainted with the pharmaceutical 
profession, might attempt to draw and pass impractical and oppres- 
sive laws ; for it can be said with certainty that the sale and consump- 
tion of habit-forming drugs will be controlled in this great country 
of ours. 



ABSTRACTS OF SOME OF THE PAPERS PRESENTED TO 
THE PENNSYLVANIA AND NEW JERSEY STATE 
PHARMACEUTICAL ASSOCIATIONS. 

By John K. Thum, Ph.G., 
Pharmacist at the German Hospital, Philadelphia. 

Unguentum Resorcini Compositum. — By William Dulin, 
Penn. Pharm. Assoc. 

After some experimentation with this ointment the author arrives 
at the conclusion that the water in the hydrous wool- fat is the cause 
of the discoloration which manifests itself after the ointment has 
been made some time ; the water dissolving the resorcin, which in 
turn exerts some action on the oil of cade. To overcome this ten- 
dency he recommends that the hydrous wool-fat be replaced by the 
anhydrous. 

AsAFETiDA. — By W. H. Pearson, Penn. Pharm. Assoc. 

When the Food and Drugs Act first went into effect there was 
considerable improvement in the quality of asafetida imported to this 
country, but after a few lots of inferior quality failed to be deported 
European merchants declared that the best grades were unobtainable 
in sufficient quantity. The author states that the motive underlying 
this plea was to influence the Revision Committee of the Pharma- 
copoeia to adopt lower standards. 

He also states that it is difficult to get representitive samples 
of this gum and illustrates as follows : A sample consisting of sev- 
eral lumps was pounded in an iron mortar till fairly uniform and the 



78 



Abstracts of Papers. 



f Am. Jour. Pharm. 
( February, 1911. 



ash amounted to 24.9 per cent., the alcohol soluble to 50.86 per cent. 
The same case was later resampled and the average of four results 
obtained indicated 54.5 per cent, of ash and only 23.2 per cent, of 
alcohol soluble material, almost the reverse of the results formerly 
obtained." 

To determine the per cent, of alcohol soluble material he puts 
10 grammes of the sample and 150 c.c. of alcohol in a mechanical 
shaker for several hours, collecting the insoluble portion on weighed 
filter paper, washes well with an excess of alcohol, and dries to con- 
stant weight at 100° C. 

Theoretically, he says, powdered asafetida should be of the same 
standard as the whole gum, but it is not convenient because of the 
moisture and volatile material that is present. If dried before pow- 
dering much volatile material is lost. He shows the loss of asafetida 
during the drying and powdering of four different lots, the average 
loss being 20.25 per cent., the loss being nearly all of the volatile and 
alcohol soluble portion, and this loss, he states, increases the ash 
and alcohol insoluble material in the finished product. 

He also says that the results of investigation of powdered sam- 
ples do not vary so much as samples of the gum because of the 
powder's comparative uniformity. 

A definite standard for the amount of soluble material in the 
tincture should be insisted upon, he states in closing. 

TiNCTURA Opii Camphorata. — By Wilbur F. Horn, 
Penn. Pharm. Assoc. 

The author is of the opinion that substituting an equivalent 
amount of the tincture of opium for the opium present in the official 
formula for camphorated tincture of opium possesses distinct advan- 
tages, such as facihty of manufacture and saving of time. 

A Method of Assaying the Ointment of Mercuric Nitrate, 
U.S. P. — By I. V. Stanislaus and E. Arthur Eaton, Penn. 
Pharm. Assoc. 

Stating that they were unable to find any assay for this oint- 
ment in either standard text-books or journals, the authors proceed 
to give a method of their own which, they remark, is accurate within 
about 0.13 per cent. 

About 3 grammes of the ointment were weighed in a beaker 



Am. Jour. Pharm. ) 
February, 1911. J 



Abstracts of Papers. 



79 



and 3 grammes of potassium hydroxide, dissolved in 35 c.c. of water, 
added. This was then heated upon the water-bath until saponifica- 
tion was complete and allowed to stand for from 24 to 48 hours, to 
allow the separation of the mercuric oxides. The mixture was then 
filtered (the filtrate being reserved to ascertain if any further deposit 
occurred). The precipitate was then washed well and transferred, 
paper and all, to an Erlenmeyer flask and 50 c.c. of nitrohydrochloric 
acid added. The flask and contents were shaken occasionally until 
solution was complete. The solution was then diluted with 50 c.c. 
of water and the paper pulp filtered off and washed well. The fil- 
trate was then evaporated to dryness in capsule, and the residue of 
mercuric chloride taken up with 100 c-c. of water and dissolved by 
the aid of heat. Hydrogen sulphide gas was next passed in until 
saturation ; the precipitated mercuric sulphide filtered off and washed. 
Next, the precipitate, paper and all, was transferred to a glass- 
stoppered bottle, an excess 30 c.c. of ^ iodine solution added and 
5 c.c. of carbon disulphide. The bottle was shaken for five minutes 
and allowed to stand for half an hour. Then the excess of iodine 
was titrated with ^ sodium thiosulphate solution." 

Some Formulas for Elixirs Proposed for Recognition in the 
Revision of the National Formulary. 

George M. Beringer, N. J. Pharm. Assn., offers some formulas 
for elixirs to be included in the next revision of the N.F. with the 
hope that they be tried and criticized by practical pharmacists. 

In speaking of elixir of calcium lactophosphate the author states 
that as the salt is now commercially obtainable a definite weight 
of it should be directed to be dissolved in aromatic elixir. The 
following formula is suggested : 

Calcium lactophosphate 25.0 Gm. 

Lactic acid 8.0 c.c. 

Aromatic elixir to make 1000.0 c.c. 

The present National Formulary formula for elixir of glycero- 
phosphates is deficient in flavoring as it contains only 300 c.c. of 
aromatic elixir. He modifies the formula and adds a requisite 
amount of compound spirit of orange. Lactic acid is used instead 
of phosphoric acid as it seems to be more effective in preventing 
precipitation of these salts. The modified formula is as follows : 



8o 



Abstracts of Papers. 



/Am. Jour. Pharm. 
\ February, 1911. 



Elixir Glycero ph osphatiim. 

Sodium glycerophosphate (75 per cent.) .... 22 Gm. 

Calcium glycerophosphate 8 Gm. 

Lactic acid 8 c.c. 

Glycerin 300 c.c. 

Compound spirit of orange 12 c.c. 

Alcohol 125 c.c. 

Purified talc 15 Gm. 



Distilled water, sufficient quantity to make. .1000 c.c. 

The author also recommends that the next revised National For- 
mulary contain a compound elixir of the various glycerophosphates 
and advises the inclusion in this book of the following formula : 

Elixir Glycerophosphatiim Compositum. 



Sodium glycerophosphate (75 per cent.). 44 Gm. 

Calcium glycerophosphate 16 Gm. 

Iron glycerophosphate 3 Gm. 

Manganese glycerophosphate 3 Gm. 

Quinine glycerophosphate 1 Gm. 

Strychnine glycerophosphate 0.125 Gm. 

Lactic acid 8 c.c. 

Compound spirit of cardamom 10 c.c. 

Alcohol 125 c.c. 

Glycerin 350 c.c. 

Purified talc 15 Gm. 



Distilled water, sufficient quantity to make 1000 c.c. 

As the formates have within recent years become exceedingly 
popular abroad, and as the British Pharmaceutical Codex has in- 
cluded formulas for elixirs and a syrup, which indicates more or less 
use in the British Isla^ids, he advises the introduction of the follow- 
ing formulas : 

Elixir Formatum. 



Potassium formate 50 Gm. 

Sodium formate 50 Gm. 

Aromatic elixir, sufficient quantity to make. . 1000 c.c. 



^Fel>lZry^lZ"" }, AbstvactS of PapCTS. 8l 

Elixir Forinatum Compositum. 

Sodium formate 32 Gm. 

Magnesium formate 16 Gm. 

Strontium formate 30 Gm. 

Lithium formate 7.5 Gm. 

Quinine formate 7.5 Gm. 

Formic acid 10 c.c. 

Compound spirit of orange - 10 c.c. 

Acetic ether i c.c. 

Alcohol 100 c.c. 

Glycerin 300 c.c. 

Purified talc 20 Gm. 

Distilled water, sufficient quantity to make. . 1000 c.c. 

The Compound Spirit of Cardamom 

called for in these formulas is as follows : 

Oil cardamom 20 c.c. 

Oil clove I c.c. 

Oil cassia 2 c.c. 

Oil orange 20 c.c. 

Oil caraway o.i c.c. 

Anethol i c.c. 

Alcohol, to make 200 c.c. 



The Need for the Practical Pharmacist in Pharmacopceial 

Revision. 

George M. Beringer, N. J. Pharm. Assoc., makes the statement 
that the development and progress made by the profession of phar- 
macy as a separate branch of medicine accounts for the increasing 
influence of pharmacists in the matter of pharmacopceial revision 
the last several decades. 

Physicians comprising the Revision Committee elected by the 
Convention of 1840 realized the value of practical pharmacists, 
asked for such aid as was needed by them in revising this book, 
and were grateful and quick to acknowledge their indebtedness. 
Following the 1840 Convention, delegates from schools of pharmacy 
and pharmaceutical societies have worked together to revise and 
produce an acceptable national standard. Fie then goes on to say 



82 



Pharmaceutical Institute. 



f Am. Jour. Pharm. 
J February, 1911. 



that there is as much need now in the revision of this book for the 
experience and practical knowledge of the pharmacist as ever be- 
fore. Formulas for the various preparations should be practical ; 
correct, both as to quantities and ingredients ; and should be work- 
able on a small scale in the average retail pharmacist's laboratory 
as well as on a large scale in that of the manufacturer. 

The Pharmacopoeia, he says in closing, can only be improved 
and brought nearer to our ideal of perfection by each one fully 
discharging his duty in connection therewith. The pharmacist has 
his share of the responsibility. He should test the formulas, report 
errors found in the book, and suggest improvements and better 
methods for exhibiting some of the remedies. 

THE PHARMACEUTICAL INSTITUTE OF THE 
UNIVERSITY OF BERLIN.* 

By M. I. WILBERT, Washington, D. C. 

As a contribution to the Centenary of the University of Berlin, 
which was celebrated in the early fall of 1910, the director of the 
Pharmaceutical Institute has compiled the story of the origin and 
evolution of the course in pharmacy at this University, from its 
foundation in 181 o to the year 19 10. 

The resulting, rather ornate, volume of 134 oblong pages also 
embodies a description of the present Institute illustrated by 
upwards of 48 photographic reproductions and diagrams. 

This latter portion of the book is particularly interesting to 
American readers because it serves to reflect, in a way not com- 
monly met with, the thoroughness and completeness of the courses 
in pharmaceutical instruction that are offered in connection with 
German universities. It also illustrates the need for assisting 
pharmaceutical schools by liberal endowments or material con- 
tributions from the general education fund, if pharmacy is to hold 
its ow^n as a professional calling and is to continue to take an active 
part in the development of the sciences that are involved. 

The University of Berlin has been particularly fortunate in 

* The frontispiece in this issue, to ilhistrate this article, was made after 
a photograph which Professor Thorns, Director of the Pharmaceutical Insti- 
tute of the University of BerHn, kindly sent to the editor of this Journal. — 
Editor. 



Am. Jour. Pharm. » 
February, 1911, J 



Pharmaceutical Institute. 



83 



its selection of men as teachers in the sciences related to pharmacy. 
The teachers who have assisted in developing the course of pharmacy 
at this university include men whose names, are widely known and 
who are generally recognized as having been active in the develop- 
ment of the several sciences in which they were specialists. 

The first teacher in chemistry was Martin Heinrich Klaproth 
( 1 743-181 3) who is generally recognized as being second only to 
the immortal Scheele in practical contributions to the pharma- 
ceutical chemistry of his day. One of his younger contemporaries 
was Sigismund Friedr. Hermbstatt (i 760-1 833) a practical pharma- 
cist who taught chemistry and pharmacy and also contributed many 
articles on pharmaceutical-chemical subjects to the literature of 
his time. 

One of the successors to Klaproth was Eilhard Mitscherlich 
(1794-1863) a student and associate of the great Berzelius and 
the discoverer of a number of now well-known chemical compounds, 
among others, of permanganic acid and its salts. Associated with 
Mitscherlich were such well-known men as Heinrich Rose (1795- 
1864) a teacher as well as an investigator, Friedr. Wohler (1800- 
1882) later the associate and successor of Liebig at Giessen, H. 
G. Magnus (1802-1870) and Gustav Rose (1798-1873). 

Among the later teachers of chemistry were such well-known 
men as E. R. Schneider, A. W. Hofmann, A.dolf Baeyer, Adolf 
Pinner, Emil Fischer, and the present director of the Institute, 
Dr. Hermann Thoms. 

The list of teachers of physics include such well-known names 
as Dove, Magnus, v. Helmholtz, Kundt and Wehnelt. 

In botany Heinr. Friedr. Link (1765-1851) was followed in 
185 1 by Alexander Braun who had as associates O. C. Berg, 
C. H. E. Koch and N. Pringsheim, all men who were able to 
leave their imprint on the progress of botany and pharmacognosy. 
Among the later teachers of botany and pharmacognosy we find 
such well-known names as Karsten, Garcke, Eichler, Schacht and 
Engler. 

These all too limited references will serve to demonstrate that 
the century of pharmaceutical instruction at the University of 
Berlin has been one of promise and possibilities despite the fact 
that for upwards of 90 years the course was severely handicapped 
by hopelessly inadequate facilities for laboratory instruction and 
even deficient provision for lectures and demonstrations. 



84 



Pharmaceutical Institute. 



( Am. Jour. Pharm. 
t February, 1911. 



The present status of the Pharmaceutical Institute of the. 
University of BerHn, on the other hand, is an excellent illu^tration 
of the benefits that may and do accrue to the community at large 
by fostering independent pharmaceutical laboratories a xl liberal 
pharmaceutical training. 

In connection with the reviews of the annual repo ts of the 
Pharmaceutical Institute of the University of Berlii tli^t have 
been published in this Journal, attention has been called to some 
of the various activities of the Institute. Not the least valuable 
of the work now done, from the viewpoint of the public health, 
is the exposing of secret or proprietary remedies that hss been 
undertaken at the request and with the assistance of the German 
Society of Apothecaries. 

The work that has been done in connection with new remedies 
is also of importance, while the original chemical and phytochemical 
investigations that have been reported have attracted widespread 
attention and have contributed much to pave the way for securing 
to pharmacy the recognition that the calling properly deserves. 

Altogether it may be pointed out that the Pharmaceutical 
Institute, as now constituted, bids fair to be an active factor in 
bringing about a realization of the possibiHties outlined by 
Fliickiger, nearly thirty years ago, in recommending the practical 
elaboration of the courses of pharmacy in connection with German 
Universities. 

In his recommendation, reproduced by Thorns in the volume 
under discussion, Fliickiger points out that many of the problems 
relating to the preservation of the public health c:.n and should be 
solved by pharmacists. 

He further points out that if pharmacists were given the 
necessary training partially or wholly at the expense of the State 
they in turn would be in position to assist, in a practical way, in 
improving the hygienic conditions of the communities in which 
they reside. 

As intimated above it is only in very recent years that the 
authorities, recognizing the possibilities of practical returns, saw 
fit to provide the necessary facilities for laboratory investigations 
and original research that are embodied in the evidently well 
equipped and truly magnificent institute at Dahlen adjoining the 
grounds of the Botanical Garden of the University of Berlin. 

For us in America the excellent work that is being done for 



Am. Jour. Pharm. 1 
February, 1911. J 



Correspondence. 



85 



the public welfare in the Pharmaceutical Institute of the University 
of Berlin should be both an inspiration and a promise. An in- 
spiration to emulate the spirit that dominated the men who through 
the many years of adversity struggled on, despite their inadequate 
facihties, instilling into their students the scientific spirit that 
dominated them and their predecessors. 

The present elaborately equipped Institute of the University 
of Berlin is a promise in that it demonstrates that properly cirected 
scientific work will and must be recognized and that pharmacy is 
assured of a promising future in all parts of the civilized world 
where its followers are earnestly and honestly laboring for the 
public good. 



CORRESPONDENCE. 

The American Journal of Pharmacy, 
145 N. loth St., Phila., Pa. 
Gentlemen : The Committee on Standards for Unofficial Drugs 
and Chemical Products are engaged in formulating standards for a 
number of articles not now recognized by the U. S. Pharmacopoeia. 
Many of the articles which they are standardizing will, no doubt, 
be admitted into the Revision of the National Formulary, now in 
process, and if the standards as promulgated by this Committee are 
adopted in that revision, then they will become the legal standards 
of the country. 

It has been suggested that a list of the monographs immediately 
under consideration should be published in the pharmaceutical 
journals so that the importers, manufacturers and dealers who are 
interested will feel at liberty to make suggestions as to the proper 
standards to be adopted. It is the desire of the Committee to be 
absolutely fair and accurate as far as possible in our work, and we 
welcome any suggestions that may be offered. The following list 
of titles covers only those on which monographs are now before the 
Committee : 

Absinthium, Aconite Leaves, Adonis, Albumen (Dried Blood), 
Albumen (Dried Eggs), Althaea Leaves, Ammonium Hypophosphite, 
Angelica Root, Angelica Seed, Areca, Arnica Root, Barium Perox- 
ide, Boldo Leaf, Bromauric Acid (Commercial Gold Tribromide). 
Buckthorn Berries, Cacao (Cocoa), Cactus Grandiflorus, Calamine, 
Calcium Glycerophosphate, Calcium Peroxide, Canella Alba, Cas- 



86 



Book Reviews. 



( Am. Jour. Pharm. 
\ February, 1911. 



carilla, Caulophylkim, Celery Seed, Centaury, Coal Tar, Cocculus 
Indicus, Condurango, Coto Bark, Cudbear, Diacetyl Morphine, Dia- 
cetyl Morphine Hydrochloride, Dextrin (White), Dextrin (Yellow), 
Euphorbia Pilulifera, Foenugreek, Formic Acid, Formic Acid (Con- 
centrated), Kava Kava, Kieselguhr, Kola, Lead Carbonate, Oil Car- 
damom, Phenolphthalein, Poppy Capsules, Potassium Glycerophos- 
phate, Quince Seed, Red Gum (Eucalyptus), Kino, Rennin, Saffron, 
Sherry Wine, Strontium Arsenite, Thuja (Arbor Vitse), Tonka 
Bean, Venice Turpentine, White Pine Bark, Zinc Peroxide. 

It is the intent to publish, from time to time, supplemental lists 
as new articles are taken up for standardization. In order to give 
the desired publicity to our work, we respectfully request the phar- 
maceutical press to give sufficient space to present this matter and 
request that any suggestions as to the proper standards to be adopted 
should be sent to the undersigned. 

Yours respectfully, 

George M. Beringer, 

Chairman. 

501 Federal St., Camden, N. J. 



BOOK REVIEWS. 

Pharmacopceia Nederlandica, Edito Quarta, Supplenda et 
MuTANDA I. Amstelodami mcmx. TJlis, the first instalment of 
additions and corrections to the fourth edition of the Netherlands 
Pharmacopoeia, published in 1905, comprises an octavo pamphlet 
of approximately 55 pages the same shape and size as the pharma- 
copoeia published 5 years ago. 

The book or pamphlet is published by the standing pharmaco- 
poeia commission and like the Netherlands Pharmacopoeia itself 
is available in both a Dutch and. a Latin edition. 

The new additions number 14 and include, Acidum acetylo- 
salicylicum, Acidum diaethylobarbituricum, Amylum Manihot, 
Antipyrinum cum Coffeino et Acido citrico, Dimethylaminoantipy- 
rinum, Emulsum Olei lecoris Aselli compositum, Extractum Cola 
liquidum, Flores Lavandulae, Hexamethylentetraminum, Semen 
Cola, Solutio Hydrochloratis Suprarenini, s-Suprareninum, Tannas 
hydrargyrosus, and Thiosulphas Natricus. 

The recognition of suprarenal alkaloid under the general title 



Am, Jour. Pharm. ") 
February, 1911. j 



Book Reviews. 



87 



s-Suprarininum with adrenalinum as a synonym is rather interest- 
ing because of the comparatively small amount of attention that 
appears to have been given this product on the Continent of 
Europe. It is also interesting to note that the Dutch title 
1-suprarenine " and the final requirement that the product on 
incineration is to leave no residue would indicate that the synthetic, 
Isevorotatory, product is preferred. 

The corrections affect no less than no of the official titles 
and are mainly changes in requirements and tests. All of the 
changes are important in that they suggest precautions that should 
be taken in connection with a work of this kind to insure fair 
and equitable standards and requirements. 

In this connection it is interesting to note that in place of 
making definite fixed requirements for the alkaloid content of 
drugs and pharmaceutical preparations the Ph. Ndl. IV now 
permits of a range of standard or a variation of approximately 20 
per cent, from the original re^quirements. 

The greater number of changes embodied in this first instal- 
ment of corrections are due to an elaboration of the requirements 
for the specific gravity of liquid preparations, usually a material 
increase of the permissible variation. 

The directions for keeping many of the official drugs and 
preparations are also somewhat elaborated, particularly in con- 
nection with narcotic leaves and herbs which are now directed to 
be protected from the influence of light. 

Apart from the changes mentioned it may be noted that the 
comprehensive and in many ways elaborate descriptions for organic 
drugs appear to be satisfactory, only one additional change being 
embodied in the present list. This change is an increase in the 
permissible ash content of lupulin from 6 to 10 per cent., making 
it similar to that of the U.S. P. 

The pamphlet, apart from the suggestions on requirements to 
be avoided or at least interpreted liberally, is a commendation of 
the care exercised by the Committee of Revision which prepared 
and published the Netherlands Pharmacopoeia of 1905. 

M. T. W. 



88 



Louis Dohine. 



J Am. Jour. Phann. 
\ February, 1911. 



OBITUARY. 

LOUIS DOHME. 

Louis Dohme, president and one of the founders of the well- 
known pharmaceutical manufacturing firm of Sharp & Dohme, 
died at the Union Protestant Infirmary, Baltimore, January 12, 
after an illness of some weeks, neuritis being the direct cause of 
his death. 

While always applying himself closely to business affairs up 
until a few years ago, Mr. Dohme was in the habit of going abroad 
during the summer for rest and recreation. Early in June last he 
made his annual pilgrimage abroad, spending the most of his time 
at the baths of Wiesbaden, where he had received benefit on a 
previous visit. On his return trip, about 9 weeks ago, he Was 
taken ill aboard the steamer, arriving in New York in an uncon- 
scious condition. From the steamer he was taken to a sanatorium 
in New York. Here he remained two weeks, making slight im- 
provement, when he was taken to the Infirmary in Baltimore, 
where it was soon realized that his condition was serious. 

Mr. Dohme was a foreigner by birth, he having been born in 
Obernkirchen, Germany, on July 6, 1837. His early education was 
obtained in a private school in his native town. When he was 
fifteen he and his five brothers and one sister were brought to 
this country by their parents, the late Charles and Sophia' Dohme. 

After attending Knapp's School, in Baltimore for several years, 
young Dohme entered the drug store of the late A. P. Sharp, where 
he soon gave evidence of those, qualities which led to the prom- 
inence and success which he attained in the chemical-pharmaceutical 
manufacturing line. While serving his apprenticeship he attended 
the Maryland College of Pharmacy, graduating in 1856 with the 
highest honors. Four years later he was taken into the firm, the 
name being changed to Sharp & Dohme. The store occupied the 
corner at Pratt and Howard Streets, a part of the present site of 
the firm, and one of Mr. Dohme's first moves after the formation 
of this partnership was to increase the capacity of the building with 
the object of engaging in the manufacture of pharmaceutical 
preparations on a small scale. When in 1866 his brother, Charles 
E. Dohme, was taken into the firm, it was decided to increase 
still further the laboratory facilities and to engage in the manvi- 



Am. Jour. Pharm. 1 
, Febraary, 1911. j 



Louis Dohme. 



89 



facture of a general line of preparations. In the division of their 
labors, Charles E. Dohme took charge of the laboratories and Louis 
began to introduce their products to neighboring physicians, 
pharmacists and wholesale druggists, finally extending his territory 
until it practically covered the United States east of the Rocky 
Mountains. It is said that Mr. Dohme made many friends among 
those he visited, and that these have remained as loyal patrons 
of the firm ever since. 

Mr. Sharp withdrew from the firm in 1885, and the next year it 
was incorporated with Louis Dohme president, Charles E. Dohme 
vice-president and Ernest Stauffen secretary and treasurer, the 
latter also having charge at present of the firm's New York office. 
Besides the officers, C. P. Dohme, a younger brother, and Dr. A. 
R. L. Dohme were included in the Board of Directors. 

Mr. Dohme was not alone interested in seeing his firm advance, 
but was active in advancing the cause of pharmacy in other ways, 
he having held several* positions of honor and trust. For some 
years he was chairman of the Board of Examiners of the Maryland 
College of Pharmacy and in 1875 was elected president of the 
College, serving in this position until 1890, when he was succeeded 
by his brother Charles E. Dohme, who held the position until the 
affiliation of the College and the University of Maryland. In igoo 
he was elected a member of the Board of Trustees of the U. S. 
Pharmacopoeial Convention. He was a member of the Maryland 
State Pharmaceutical Association and a life member of the 
American Pharmaceutical Association, and a member of the social 
clubs, the Germania and Country Clubs of Baltimore. He was 
fond of art and literature, and devoted much of his spare time to 
the reading of the classics. 

Mr. Dohme was unmarried, and had made his home for the 
past 25 years with his brother, Charles E. Dohme, at 822 North 
Carrollton Avenue. His funeral was held here. 

He is survived by two brothers — Messrs. Charles E. and William 
F. Dohme. He also left six nephews — Drs. A. R. L. and Gustavus 
C. Dohme; Messrs. Justus Dohme, C. Louis Dohme, of Culpeper, 
Va.; William I. F. Dohme, of Montclair, N. J., and Carl A. G. 
Frisius — and six nieces — Misses Adele C. Dohme, Clara Dohme, 
Nettie Dohme, of Montclair, N. J.; Mrs. Charles G. Holzhauer, 
of Newark, N. J. ; Mrs. Alma Von Marees and Miss Agnes Frisius. 

A portrait of Louis Dohme is given in the frontispiece of the 



90 Philadelphia College of Pharmacy. {^Yv^^mlly^inT' 

June, 19 1 o, issue of this Journal, as one of the members of the 
Board of Trustees of the U. S. Pharmacopceial Convention of 1890. 



PHILADELPHIA COLLEGE OF PHARMACY. 

MINUTES OF THE QUARTERLY MEETING. 

The quarterly meeting of the College was held on December 
27th, 1910, at 4 P.M. in the Library. Eleven members were present. 
The President, Howard B. French, presided. The minutes of the 
semi-annual meeting held September 26, were read and approved. 
The minutes of the Board of Trustees for September, October, and 
November, were read by the Registrar, and approved. 

The President appointed the following members as the Perma- 
nent Committee on Centenary Celebration of the College, George 
M. Beringer, Chairman, Joseph P. Remington, Henry Krsemer, 
Samuel P. Sadtler and M. I. Wilbert ; and on the Committee on 
Legislation, Joseph P. Remington, Chairman, M. I. Wilbert, 
William Mclntyre, Warren H. Foley, Theodore Campbell and 
Charles Leedom. Professor C. B. Lowe presented through J. M. 
Maris & Co. a small ground stopper bottle which was formerly 
used in the store of the late Charles A. Heinitsh, of Lancaster, 
and said to be one hundred and thirty years old. The thanks of 
the College were tendered the donor. 

The President appointed Joseph W. England, George M. 
Beringer, and Joseph P. Remington a committee to draft suitable 
resolutions on the death of Professor Hallberg, and to report to 
the meeting of the Board of Trustees to be held on January 3, 191 1. 



Abstract from the Minutes of the Board of Trustees. 

September 6, 1910. Sixteen members present. Mr. Wallace 
Procter, an ex-member, was also present. The Committee on 
Announcement reported the issue of Bulletin No. 4, Vol. 2 ; also 
that a Spanish edition of the Bulletin was being prepared. 

Mr. French read a communication from the executors of the 
estate of Robert W. Johnson, relative to the legacy left by him to 



^FebraaS^mr*} Philadelphia College of Pharmacy. 91 

the College. He also read the bond necessary to be filled out, 
upon receipt of which the legacy would be paid. 

Mr. England read several communications relative to the mail- 
ing of periodicals issued by the College, which were referred to 
the Committee on Publication for their consideration, and to be 
reported on to the College. 

Mr. Clifife read a communication relative to entrance examina- 
tions, which was referred to the Committee on Instruction. 

October 4, 19 10. Fourteen members present. The Committee 
on Property reported the changes made in the Pharmaceutical 
Laboratory and on the fifth floor, the latter giving a suitable room 
for physical training. Mr. Clifife reported that the Director, Dr. 
Schleif, and Instructor, Mr. Beam, considered the room well lighted 
and ventilated, and when equipped would prove one of the best 
gymnasiums in the city. 

Committee on Library reported, Librarian, Miss Katharine E. 
Nagle in charge, and the Committee on Examinations reported 
that James Henry Allen, Frank Earl Haines, and Miss Aase Teisen 
had satisfactorily passed all examinations in the Course for the 
Certificate of Proficiency in Chemistry, and that Peter Amsterdam 
had satisfactorily passed the examination for the Certificate of 
Proficiency in the Food and Drug Course ; and these certificates 
were accordingly awarded. 

Committee on Announcement reported that the Special Bulletin 
relating to the course of instruction in Analytical Chemistry and 
Food and Drugs course was in press, and that the Spanish edition 
was being printed. 

Committee on Commencement reported that the Academy of 
Music had been leased for May 25, 191 1. 

Committee on Scholarships recommended the names of eleven 
students to receive the various scholarships available, and the 
recommendations were approved. 

A communication from the Board of Education was read 
recommending a graduate from the Central High School, and 
one from the Northeast Manual Training School for scholarships, 
and these recommendations were approved. 

A communication was read from H. H. Cregg, of the Class of 
1883, requesting a duplicate diploma, which w^s granted under 
the usual condition. 



92 Philadelphia College of Pharmacy. {^tanZly^ioiT' 

A coninumication was read from the Secretary of the State 
Board of Pharmacy relative to a Certificate of Actual Attendance 
at the Lectures and Laboratories of those graduates of the College 
who desire to take the examination for Registered Pharmacist. 
After considerable discussion, a committee consisting of Professors 
Remington, Sadtler, and Lowe, was appointed to formulate and 
put in effect such a method. 

November i, 19 lo. Twelve members present. 

Committee on Library reported a decided improvement in 
the work and management of the Library. Library rules also the 
State law relative to mutilation of books and library property 
wTre displayed in the Library. 

Committee on Instruction called attention to the Special 
Lectures arranged for 1910-1911, and urged that the attention of 
the students, especially the graduating class, be directed to these 
lectures. 

Committee on Announcement reported that the October 
Bulletin, No. i, Vol. 3 was ready for distribution. 

Communica-tions were read from students to whom scholarships 
had been awarded, expressing their appreciation. 

A communication from the Board of Education was read, 
recommending Karl N. Krogh, a graduate of the Southern Manual 
Training School, as worthy of a scholarship, and on motion, this 
award was made. 

The Treasurer reported that five thousand dollars ($5000) had 
been paid on account of the mortgage. 

C. A. Weidemann, M.D., 

Recording Secretary. 

December Pharmaceutical Meeting. 

The regular Pharmaceutical Meeting of the Philadelphia College 
of Pharmacy was held on Tuesday afternoon, December 20, 1910, at 
3 o'clock, Mr. E. M. Boring presided. 

Mr. Clarence M. Kline read a paper on The Thirty-Sixth 
Annual Meeting of the National Wholesale Druggists' Association 
held at Dallas, Texas, November, 1910," which will be published 
in a later issue of this Journal. The paper was discussed by Pro- 
fessor Kraemer, Dr. C. B. Lowe, Mr. Kline, and the chairman. 

Mr. Kline submitted a copy of that portion of the General Code 



^F;braa^vfi9ir'} Philadelphia College of Pharmacy. , 93 

of Ohio relating to paints, white lead and turpentine. Its provisions 
are as follows : 



Sec, 6331. No person, firm or corporation shall expose for sale or 
sell within this state, paint, turpentine or linseed oil, which is labeled 
or marked so as to tend to deceive the purchaser thereof as to its nature 
or composition, or which is not labeled as required by this chapter. 

Sec. 6331 -I. No person, firm or corporation shall manufacture, mix 
for sale, sell, offer for sale, for other than medicinal purposes, under the 
name of turpentine, or spirits of turpentine, or any compounding of the 
word turpentine, or under any name or device illustrating or suggesting 
turpentine, or spirits of turpentine, any article which is not wholly distilled 
from rosin, turpentine gum, or scrap from pine trees, and unmixed and 
unadulterated with oil, benzine or any other foreign substance of any 
kind whatsoever, unless the package containing same shall be stenciled 
or marked, with letters not less than two inches high, adulterated 
spirits of turpentine. Nothing herein contained shall be construed as 
prohibiting the manufacture or sale of any such compound or imitation, 
providing the container shall be plainly marked, and the purchaser notified, 
as aforesaid. 

Sec. 6332. The term " paint" as used in this chapter shall include 
oxide of zinc, red lead and white lead, dry or in any kind of oil, and 
a compound intended for like use, colors ground in oil, paste or semipaste 
paint, and liquid or mixed paint ready for use. 

Sec. 6s33. The label required by this chapter shall clearly and distinctly 
state the name and residence of the manufacturer of the paint, or of the 
distributor thereof or of the party for whom it is manufactured, and show 
the name or names of any substance or substances used in quantities 
sufficient to be dangerous or injurious to human life or health whether 
through absorption, contact or inhalation. The label shall be printed in 
English language in plain legible type in continuous list with no intervening- 
matter of any kind. 

Sec. 6334. The label on paint sold by measure shall show the net 
measure of the contents of the container, and on paint sold by weight, 
the net weight of the contents of the package. 

Sec. 6335. The possession of an article or substance improperly 
marked or inaccurately labeled as provided in this chapter, by a person, 
firm or corporation dealing therein shall be prima facie evidence that it 
is so kept in violation of this chapter, and the penal statutes relating thereto. 

Sec. 6336. The dairy and food commissioner of Ohio shall enforce the 
provisions of this chapter and the penal statutes relating thereto, and such 
commissioner, his assistants, experts, chemists and agents shall have access 
and ingress to the places of business, stores and buildings used for the 
sale of paint, turpentine or linseed oil, and may open any package, can, jar, 
tub or other receptacle containing an article that may be sold or exposed 
for sale in violation of such provisions or statutes. The inspectors, assistants 



94 Philadelphia College of Pharmacy. \^vkiZ\-y%T' 

or chemists appointed by such commissioner, shall perform like duties and 
have like authority under this chapter and the penal statutes relating 
thereto as is provided by law in other cases. Such commissioner shall 
publish bulletins from time to time giving the results of inspections and 
analyses, with such other information as he deems suitable. 

Sec. 13168. Whoever violates any provision of the law relating to 
the labeling of paints, mixed paints and similar compounds or white lead 
by manufacturers or distributors thereof, shall be fined not more than fifty 
dollars, and for each subsequent offense, shall be fined not less than fifty 
dollars nor more than one hundred dollars, or imprisonment not less than 
thirty days, nor more than one hundred days, or both. 



Professor Remington presented, on behalf of E. M. Roche, a 
pharmaceutical recipe book. 

Professor Kraemer exhibited the " Tabloid" Photographic Outfit 
no. 906," put up by Burroughs Wellcome & Co. This comprises a 
compact ecjuipment of Tabloid" photographic chemicals for de- 
veloping and fixing plates, films, papers, and lantern slides ; and 
also Tabloid" chemicals for intensifying, reducing, sepia toning, 
copper toning, hardening, clearing, restraining, etc. Sufficient 
chemicals are provided to make several gallons of solutions in 
large or small quantities, fresh and vigorous for each occasion, 
without the trouble of weighing and without waste. A copy of 
the Wellcome Photographic Exposure Record and Diary, a com- 
plete pocket guide to success in field and dark room, is also included. 
The whole is packed so as to be convenient in travelling. 

Professor Kraemer stated that he had found the Wellcome 
Photographic Exposure Record and Diary a convenient book for 
recording field work in photography and the Wellcome Exposure 
Calculator very useful in determining the time exposure to be given. 

On account of the difficulty in making good photographs, due 
to the difficulty in estimating the proper exposure, this book with 
its simple instructions should prove of great service to the pho- 
tographer, no matter where or under what condition exposures are 
made. Again as it is frequently desirable to develop the plates before 
returning home, this compact equipment of photographic chemicals 
supplies a want which will be appreciated by photographers who 
are making exposures away from home. 

A complete collection of ground emery samples, received from 
Walter C. Gold, of Philadelphia, were presented on his behalf by 



Am. Jour. Pharm. } 
February, 1911. j 



Correspondence. 



95 



Professor Kraemer, who also called attention to a specimen of the 
Jungle Plant/' C ombre turn simdaicmn, which he had received 
from a fellow member, Henry C. Blair. 

George C. Goess, of Philadelphia, presented a bottle of Church's 
Cough Drops which sample is said to be 120 years old. Professor 
Kraemer remarked that it might be of considerable interest in the 
years to come if the College had a collection of Proprietary Medi- 
cine, many of which in a few years would probably be no longer 
obtainable, and that the interest in them would lie chiefly in their 
illustrating a method of medication in vogue at a particular period. 

Mr. Henry C. Blair presented an excellent specimen of bauxite 
from Georgia and a unique specimen of wood carving representing 
the seven idols of China, each idol being from 3 to 5 cm. long. 

President French presented a collection of silver ores which he 
obtained during a recent trip to Colorado. 

Mr. E. H. Eppler, of Philadelphia, presented a hand balance 
which was used by Professor Maisch in his old store at 1610 Ridge 
Ave., Philadelphia. 

A vote of thanks was tendered the donors for the various articles 
presented to the College as also to Mr. Kline for his communi- 
cation. 

H. K. 



CORRESPONDENCE. 

U.S. P. & N.F. Compulsory in New York State . 

To The Editor of The American Journal of Pharmacy. 

Sir : Attention is called to the change of rules by the New State 
Board of Pharmacy and approved by the regents that every pharma- 
cist and druggist in the State of New York must possess a copy of 
the latest edition of the U.S.P. and N.F. 

The rule of the old Board required a copy of the U.S.P. or some 
other publication embodying its text in full. Rule 7 of the New 
State Board of Pharmacy reads as follows : 

" Every pharmacy and drug store shall own and have on file at 
all times the eighth decennial revision of the Pharmacopoeia and the 



96 



Correspondence. 



j Am. Jour. Pharm. 
\ February, 1911. 



latest edition of the National Formulary and no registration cer- 
tificate shall be issued till it complies with this rule." 

It is of course also advisable to have a dispensatory as a reference 
book in well regulated pharmacy. As the rule is very likely to be 
enforced I earnestly advise your subscribers in New York State to 
supply themselves with copies of the N.S.P.VIII and N.F.III which 
books can be obtained readily through the wholesale drug trade. 

Let us hope that other State Boards of Pharmacy will follow 
this example, in fact that State Laws will be enacted and enforced 
making the possession of a copy of the latest edition of the U.S. P. 
and N.F. compulsory in every pharmacy and drug store in the U.S. 

Otto Raubenheimer, Ph. G. 



THE AMEEIOA]Sr 

JOURNAL OF PHARMACY 



MARCH, igii 



THE BIOLOGICAL STANDARDIZATION OF DRUGS. 

By Worth Hale, M.D., 
Assistant Pharmacologist, Hygienic Laboratory, U.S.P.H. and M.H. 
Service, Washington, D. C. 

Pharmacy calls for accuracy as applied to remedial agents. 
Absolute and unfailing accuracy to the limits of scientific knowl- 
edge and unvarying honesty are fundamental principles to be 
emphasized and dwelt upon from the beginning of a course in 
Pharmacy or of medicine, until the last prescription is compounded. 
There should be no guess work and every effort on the part of 
pharmacist or doctor or laboratory worker to promote greater 
exactitude so far as drugs and medicines are concerned is to 
advance the heaHng art. Nor is it an unworthy ideal for careless- 
ness in the field of drugs and medicine is scarcely less dangerous 
than for railroad engineers to guess at the color of signals and 
there is no questioning that hundreds of people are annually killed 
because such haphazard and commercial methods have been used 
in preparing drugs that they do not have the virtues expected of 
them. 

We too often forget that not only medicine but also pharmacy 
is a business dealing in life and health. It is trite to say that 
human life often hangs upon a thread and that the merest in- 
cident may determine the issue ; that the failure of a drug to 
have the strength it is supposed to have because of impurity or 
dangerous deterioration or adulteration or lack of active principles 

(97) 



98 Biological Standardization of Drugs. ^^u^' 

means delayed convalescence or even death, (i) These are state- 
ments which may sound a trifle theatrical. One can not often 
prove them. If a patient is made more violently ill or dies no 
one suspects that the medicine was at fault. It is a visitation 
of providence or, as the facetious would have it, a doctor was 
called and then the undertaker. 

My attention has recently been called to a case of poisoning. 
The patient, who suffered from chronic heart disease, had been 
receiving tincture of strophanthus in a certain dose. The prescrip- 
tion was refilled and the medication continued. After the second 
dose from the new strophanthus tincture poisonous symptoms 
rleveloped although fortunately ultimate recovery ensued after two 
days of serious illness. An assay made at this laboratory of the 
strophanthus showed that it was an exceeding*ly active preparation 
and whereas the patient was supposed to be receiving the same 
dose as of the old he actually received an amount of the active 
principle in this new preparation equal to about three times that 
of the strophanthus tincture which he had formerly been taking. 

In the opposite direction I have a report on a digitalis prepara- 
tion which upon examination proved to be distinctly depressing to 
the heart and not a tonic. Who would dare say that the administra- 
tion of this drug to an already overburdened heart would not 
produce the most disastrous results. A physician in Baltimore 
made inquiry of the firm exploiting this preparation. The firm 
replied that we had made an effort to secure an old and deteriorated 
sample for our examination. Like certain other extravagant claims 
made by an occasional manufacturer this statement was a bald 
untruth to save their own reputation and was absolutely without 
foundation. The facts are that the original bottle was ordered 
by our pharmacist from a local jobber and the jobber had no 
information whatever that the drug was to be tested. It was 
just such a bottle as would have been dispensed on a physician's 
prescription. 

Upon facts such as these, and the number of specific instances 
could be multiplied almost indefinitely, the whole theory of drug 
standardization rests. Any consideration of quality from a com- 
mercial standpoint is wholly secondary and drugs should be stand- 
ardized or assayed that the patient may receive of potent remedies 
always and invariably the amount of active substance prescribed : 
and when this has been done the pharmacist has given the best 



^"Mirch'mr"^™'} Biological Standardization of Dmgs. 99 

of his skill as an aid to that of the physician to the cure of the 
sick. 

The committee in charge of the revision of the recent editions 
of the pharmacopoeia have clearly recognized the need for suit- 
able standards especially for the more potent drugs in order to 
eliminate the danger and inaccuracy in the administration of 
remedial agents. Thus in the sixth and seventh and eight re- 
visions of the Pharmacopoeia we find tests and assay processes 
introduced while in the Eighth revision a further notable advance 
was made, in the adoption of a standard for diphtheria antitoxic 
serum. There are a number of very important drugs long used 
in medicine and more recently also certain biological products for 
which chemical tests or assay methods are not available owing to 
the fact that the chemistry of these substances either is not known 
or they are of such a character that quantitative m,ethods can 
not be successfully employed. For these, biological tests and 
standards have been proposed although excepting that for diph- 
theria antitoxic serum none have as yet been officially adopted. 
The recent Pharmacopoeial convention however adopted a general 
principle reading as follows : 

" It is recommended that biological tests or assays, when ac- 
curate and reliable, may be admitted.^' 

In the group of drugs for which chemical standards are not 
at the present time available are digitalis, strophanthus, convallaria, 
squills, apocynum, preparations of the suprarenal glands, ergot, and 
cannabis indica. 

It is somewhat surprising in view of the great importance of 
some of these drugs that, although biological tests were proposed 
nearly 50 years ago, no practical application was miade until 
1898. I am informed that Professor Cushny first suggested such 
standardization especially for the digitalis group but the first paper 
relating definitely to the subject was one in October, 1898, by 
Houghton who worked in Cushny's laboratory. Since Houghton's 
paper the subject of Biological Standardization has attracted a 
good deal of attention from pharmacologists and more recently 
also from progressive drug manufacturers and pharmacists. 

The drug, or rather group of drugs, upon which the most 
work has been done is the digitalis group, it being generally con- 
ceded that a method applicable to one member as digitalis itself 
would be applical)le equally to strophanthus or squills. As a result 



loo Biological Standardization of Drugs, {^^t^uj^n"^' 

no less than 15 or 20 methods have been proposed for their assay. 
So much discussion of these metliods has been indulged in and 
so many statements more or less supported and often unsupported 
by experimental evidence have been offered by the exponents of 
a particular method that it seems worth while to take up the 
various phases of the problem at this time, and this especially 
because of the possible, and I hope probable, adoption of some 
method by the committee of revision of the next Pharmacopoeia. 

If accurate and reliable are the modifying phrases in the recom- 
mendation of the Pharmacopoeial Convention regarding biological 
standards. How accurate; How reliable — Digitalis preparations, 
tinctures, fluidextracts, tablet triturates, and hypodermic tablets, as 
purchased direct from the manufacturers, vary about 400 per cent, 
in activity. Is the revision committee willing to adopt any method 
which will reduce this enormous variation to 50 per cent? I am 
absolutely certain it will mean that lives will be saved every year. 
If any biological method will reduce the variation of the prepara- 
tions on the market to 25 per cent, instead of 400 will it be worth 
while? Will it be accurate enough? I would much prefer that 
I myself should be assured by the Pharmacopoeia of a drug with 
no more than 25 per cent, variation rather than to tbke my 
chances with a drug now of one strength and on a refilled pre- 
scription one or four times the strength. 

In this country four methods have been proposed, namely, 
Houghton's twelve hour frog method, Reed and Vanderkleed's 
method using the guinea pig, a method proposed by Hatcher 
using the cat ; all of these methods depending on the determination 
of the least fatal dose for the animal in question, and finally the 
method proposed by Famulener and Lyons, that of determining 
the least amount of the drug to stop the heart of a frog in o-ne 
hour. 

Houghton's method is to choose frogs of about the same weight 
and inject them with a given amount of the drug. If, at the 
end of 12 hours, the animal is dead the dose is reduced, if alive 
the dose is increased. By use of a series of frogs with varying 
doses the assay may be hastened. An experiment published in the 
American Journal of Pharmacy indicates that 3 days were 
required to make the assay, and the assay required the use of 
14 frogs, the cost of which in any section of the United States 
including express charges would be under one dollar. In Washing- 



I 



^"kfrch'mr""'} Biological Standardisation of Drugs. loi 

ton the cost would be 60 cents for frogs shipped 800 to 1000 
miles. 

Reed and Vanderkleed's method of assay is probably w:ell 
known to you. I quote from a recent article by Githens and 
Vanderkleed. " Guinea pigs are first weighed and then to one pig 
is given hypodermically the standard minimal fatal dose as deter- 
mined by a large series of experiments on guinea pigs, to a second 
9/10 of this, and to a third ii/io. If the drug is of the proper 
strength the two pigs receiving the larger dose will die, the third 
will recover. If two pigs live the dose is increased by tenths 
until two die. If all three die the dose is reduced by tenths until 
a pig lives." The cost of animals at Washington would be not 
less than $2.00 and the assay would take, I presume, about a 
day. However, in testing out this method for myself the smallest 
number of animals used in an assay was 7, the largest number 18, 
the average of the test of 8 different preparations being 11 which 
would cost us $5.50 per assay and the time required would be 
extended to at least two days. Further, certain animals survived 
doses 20 per cent, larger than had killed others. Thus, 4 were 
killed with 0.5 mgm. per gram body weight, 3 lived with 0.6 
mgm. doses of the same drug. 

Hatcher's method is the most complex of all although he sug- 
gests that the retail pharmacist would find it available for his use 
on account of its simplicity. That certainly will make it appear 
attractive even though it is undoubedly the most difficult of all 
the American methods. 

In this method a cat is anaesthetized, the femoral vein is ex- 
posed and a cannula introduced. Then into this the digitalis 
preparation is slowly injected and the injection stopped or con- 
tinued slowly when toxic symptoms such as irregularity of the 
heart and respiration, convulsions, etc. are seen ; the end reaction 
is the death of the animal. 

A modification of this method is to inject about 75 per cent, 
of the supposed fatal dose which is followed by the injection of 
ouabain which acts like digitalis but more rapidly until toxic symp- 
toms appear, the drug is then continued more slowly until death 
results. P^or this method an accuracy of within 3 per cent, has been 
claimed, but from later investigations Hatcher says a number of 
cats have been found which tolerate doses nearly 50 per cent, more 



102 Biological Standardization of Drugs. { ^^ilSl"; i?i l 

than in his earher experiments. In inexperienced hands the 
variation would probably be even greater. 

These methods all depend on the estimation of the least fatal 
dose, but for reasons to be given such an end reaction appears 
tO' me to be undesirable. Digitalis glucosides act not only on 
the heart but also directly on the central nervous system first 
stimulating and then depressing it. In these general toxic methods 
the drug is given in sufficient doses to cause death without refer- 
ence to the organs chiefly affected and no one can say, although 
much theorizing has been indulged in, whether the death is the 
result of an action on the heart or on the brain or, and I think it 
extremely likely, a resultant of the action on both brain and heart. 

The method is usually carried out using mammals and while 
this is believed by some to be a step in the right direction on 
account of the closer relation between the higher animals when 
compared to cold-blooded animals (frogs) and man certain experi- 
mental evidence tends to show that this is not necessarily so. 
At least it is to be noted that death in such animals in certain 
cases apparently resulted fromi a paralysing action on the central 
nervous system while the heart as recorded by blood pressure 
tracings was still in good condition. In other cases the respiratory 
movements were kept up some time after the heart had stopped 
beating and the blood pressure had fallen to zero. Further the 
allegation that these effects on the central nervous system are all 
secondary to the heart action is contrary to^ the known facts of 
Physiology. 

In this connection it is further urged that a digitalis preparation 
with a high percentage of the saponin like body, digitonin, would 
easily cause death from the action of this poison which depresses 
both the heart and the central nervous system. Thus such a 
preparation would probably show a high value by a general toxic 
method although the heart tonic principles mig'ht be present in 
relatively small amounts, or of two preparations with the same 
proportion of substances acting on the heart that with the larger 
amount of the saponin like body would assay stronger. In the 
general toxic method in which frogs are used, as in Houghton's 
twelve hour method," this objection would naturally lose some 
weight on account of the ability of such animals to live a con- 
siderable time independently of the central nervous system, the 
action of the drug being therefore presumably upon the heart. 



^""'Marcii im™' } Biological Standardization of Drugs. 103 

As a further objection it may be suggested also that a general 
toxic method would not show adulteration or accidental contamina- 
tion of a digitalis preparation since a lethal effect could easily be 
secured from an action of any of a number of poisons or possibly 
also from substances formed in the deterioration which digitalis 
preparations are known to undergo. To be certain of a heart 
tonic, a digitalis action, such a method would need to be controlled 
by tests upon the heart itself. 

The other type methods are based on a general principle which 
it would seem worth while emphasizing — namely, that any biological 
assay method for any drug should take into account that action 
of the drug upon zvhich its chief therapeutic usefulness rests and 
that in so far as practical difficulties did not interfere this action 
should he made the basis of the biological method used in its assay. 
In the case of the digitalis group it would seem of considerable 
importance, if this be true, that the end reaction should be one 
involving the characteristic effect of the group upon the circulation 
apparatus and this can be done on mammals only by making use 
of recording devices and maintaining artificial respiration. 

The type method of determining the comparative value by 
noting their effects upon the heart, especially of the frog, is per- 
haps the oldest and at the present time the most widely used of 
all methods as it is used by at least three manufacturers in this 
country and exclusively in Germany. 

Three sub-methods may be described although others are occa- 
sionally used ; in one the drug is given to the intact animal which 
is subsequently operated on to note the condition of the heart, in 
another the drug is given to the animal subsequent to the operative 
procedure in which the heart is exposed. In the third the heart 
is removed from the body and perfused ; however, the last named 
methods are not used in this country and will not be discussed 
on that account in this paper. 

The first sub-method, that of examining the heart at some 
time subsequent to the injection of the drug, the chief points of 
differences in the manner of experimicntation has been in the time 
at the end of which the heart of the frog should be found in com- 
plete systole. Time limits varying from thirty minutes to two 
hours have been used. 

This method has been provisionally adopted at this Laboratory 
for testing digitalis and allied preparations. The general method 



I04 Biological Standardisation of Drugs. { ^'^ardi,* im" 

of procedure is essentially the same as that suggested by Famulener 
and Lyons ^ in which permanent systole of the frog's ventricle 
at the end of exactly one hour is taken as the end reaction. Some 
slight modifications have been • made, the chief of which is that 
the assays are all carried out at a constant temperature as it is 
believed that this precaution results in greater accuracy. The 
drug is injected through the mouth into the anterior lymph sac 
of the intact frog (Rana pipiens) and at the end of an hour the 
animal is pithed (both brain and cord) and the thorax opened. 
The condition of the heart is then noted and a smaller or larger 
dose is injected as indicated. To hasten the assay a series of 
three frogs is usually given doses which vary quite widely and 
an approximate dose is estimated from these preliminary results. 
By successively narrowing the limits of dosage that amount just 
necessary to produce the end reaction may be determined by the 
use of from 8 to 12 frogs. 

The method has the advantage of comparative simplicity so 
far as operative technique is concerned. The animals are always easily 
obtained which is a very important consideration and if the storage 
tanks be kept at a suitable temperature (10° to 15° centigrade) 
they remain active and healthy for months. In this connection 
it is worth while calling attention to the difificulty of obtaining 
a suitable number of mammals, especially cats, rabbits, or dogs, 
for carrying out such tests on warm blooded animals when a large 
number of assays are to be made. Of less importance also is that 
of cost. Frogs for each assay will cost approximately fifty cents. 
If mammals are used, on the basis that at least three to five should 
be used for each assay, the cost would be from two to three 
dollars while tO' this would be added the expense of food supplies, 
etc., which in the case of the higher animals is a considerable 
item. 

While thus expressing my belief in the frog as a suitable and, 
despite certain elemental precautions, a convenient animal for assay 
purposes it has never been shown to what degree biological assays, 
using either frogs or other animals, were accurate and especially 
as showing the therapeutic potency of a given preparation. 

Unknowns made up by a chemist in the Division of Pharma- 
cology were assayed and the results of these assays are grouped 



'Famulener and Lyons: Proc. Am. Pharm. Ass., 1902, 50, 415. 



^™Maix*h ■ mr"^' } Biological Standardisation of Drugs. 105 

together in the following table not only as a means of comparing 
the activities of the various so-called pure principles but also to 
show^, in tabular form, the amount of error which is to be expected 
when using a frog-heart method of assay. 

Drug Assay Value ^ Unknown Solutions per cent, error. 





1910 


1902 ^ 


I 


2 


3 


4 


Strophanthin 


0.000,001,10 


0.000,000,5 


1.8 


2.9 


3-1 


1.4 


Convallamarin 


0.000,004,75 


0.000,004,5 


8.6 


10.6 


74 


9.0 


Digitoxin 


0.000,008,50 


0.000,008,5 


7.2 


3.8 


0.7 


5-2 


French Digitalin 


0.000,013,00 


0.000,015 


1.6 


3-8 


3.6 


2.6 


Digitalein 


0.000,024,00 


0.000,032,5 


4-5 


3-8 


6.0 


1.5 


German Digitalin 


0.000,070,00 


0.000,022,5 


2.5 


2.8 


5-9 


0.0 



From this summary it is apparent that strophanthin is the most 
active, the German digitalin (Digitalin purum Griibler) is the 
weakest and that digitoxin the most active of the digitalis glu- 
cosides, is about 8 times less active than amorphous strophanthin. 
It is not urged on the basis of these experiments, however, that 
in the clinical use of these substances doses be given proportionate 
to these values. But in so far as secondary factors, such as rate 
of absorption and elimination, do not interfere proportionate doses 
would probably give like therapeutic results. Elemental tissues 
such as the heart muscle, no matter from what animal species, 
react qualitatively the same. As pointed out by Cushny * the 
action of the digitalis group upon the frog's heart is strictly anal- 
ogous to the action on the mammalian heart with differences in 
action, dependent upon a stronger vagus activity in the higher 
animal species. In the therapeutic use of the drug only the first 
stage which consists of a minimal activity of the vagi and a 
definitely increased activity of the muscle substance itself is desired. 
The action on the frog is almost purely a muscle action and it is 
upon such grounds that biological assay methods on the lower 
forms of animal life are believed to give results which are capable 
of direct utilization in therapeutics. 

On theoretical grounds, therefore, there is no reason why assays 
using frogs will not give results which may not be depended 

^Amount in gram per gram body weight of Rana pipiens to cause 
permanent systole of the ventricle in one hour. 
^ Famulener and Lyons. 

* Cushny : Pharmacology and Therapeutics, 1906, p. 466. 



io6 Biological Standardization of Drugs. {^\tZ[ i<i\T'' 

on by the clinician and which may be used as a basis for dosage 
as safely as if assays were carried out on guinea-pigs, rabbits, 
cats, or dogs and so far as the evidences of accuracy and totality 
of action go far more safely than ' if carried out by estimating 
the single active constituent digitoxin or digitalin by chemical 
means. Assays, as is to be noted by the above summary, may be 
made using frogs (possibly also other animals) which will give 
an estimate of the amount of glucosides in a solution to within a 
few (i to lo) per cent, of absolute accuracy. 

In all cases in therapeutics the unknown factors of absorption, 
elimination, and susceptibility will persist in spite of all attempts 
at assaying the preparations of the digitalis group. But these 
factors would also exist in like degree as long as several differently 
active bodies and resinous substances are to be reckoned with even 
if absolute chemical assays of not one but all the active glucosides 
of the group were possible. The frog method of assay gives all 
any assay method can possibly give, that is, a definite index of 
the amount of active substances, and what is especially important 
an index of the activity of all substances in the preparation which 
act upon the heart. 

Certain factors regarding variation in reaction of frogs to the 
digitalis group of glucosides, or to other poisons, are of little 
importance aside from increasing to a very slight degree the com- 
plexity of the assay process. The whole question resolves itself 
into a matter of using a digitalis preparation of known activity 
and keeping quality (and for this purpose crystallized digitoxin 
or ouabain is suggested) to standardize the frogs at the same time 
that the unknown is assayed. In this way accurate results max 
be obtained without reference to season, age, sex, temperature 
conditions, or species of frogs used. 

I have purposely discussed at some length the frog-heart method 
as proposed by Famulener and Lyons and it may be regarded some- 
what as a personal matter with me since I use it that I should 
give it so much time. T have tried not tO' make it so and have 
approved of it because in my best judgment it was based on per- 
fectly sound physiological facts as well as experimental evidence 
for, excepting Hatcher's cat method, all these methods have been 
reviewed after personal investigation and the whole matter con- 
sidered as impartially as possible previous to its adoption. It is a 
fact, however, that long acquaintance with a particular method 



^™kirch 191^™" } Biological Standardisation of Drugs. 107 

is apt to lend some bias to one's judgment and also because of 
longer experience one naturally obtains more uniform with the 
method he is accustomed to use. 

I wish to go on record, however, as believing that the adop- 
tion of any one of these methods will give to those who need 
digitalis medication a vastly more uniform drug than is now ob- 
tainable. Absolute accuracy cannot be expected, but there can 
be no question that a comparatively accurate assay of digitalis is 
possible with variations not exceeding 10 per cent, in the thera- 
peutic activity of the drug. 

Ergot : 

Ergot, the drug next in importance to the digitalis group, is 
used especially at child birth to promote contraction of the uterus 
and to thus prevent dangerous and even fatal hemorrhage. At 
the present time there is no known way to assay ergot accurately 
by chemical means, but it is known from clinical as well as physio- 
logical tests that many samples of ergot on the market are absolutely 
devoid of a typical ergot action, thus often exposing mothers to 
one of the most feared accidents of child bearing. 

The chemistry of ergot is becoming better known and at the 
present time some five active constituents have been pretty cer- 
tainly isolated in a pure state. These are ergotoxine and ergo- 
tinine, which are characteristic of ergot, parahydroxyphenylethyl- 
amine, betaimidoazolylethylamine, and guanidobutylamine — the 
amines being found also in other places as in the decomposition 
of meats. Of these, ergotoxine causes a marked contraction of 
the pregnant uterus and also- a certain amount of contraction of 
the non-pregnant organ. In addition it also causes bluing and 
gangrene of the cock's comb and causes an increase of blood 
pressure. Ergotinine has little or no activity but is closely related 
chemically to ergotoxine. One of the amines causes a rise in 
blood pressure, another a fall, but both cause contraction of the 
non-pregnant uterus. It has by no means been clearly established 
what their effect is upon the pregnant organ. The third amine 
has not been tested physiologically. In addition there is no reason 
to believe that there may not yet be some half dozen other bodies 
all with more or less action on the uterus. 

For digitalis chemical methods may at some time be available, 
but it seems absolutely unlikely that a chemical assay will ever 



io8 Biological Standardization of Drugs. {%S:mr"' 

show the therapeutic activity of ergot. Biological tests, however, 
have been used for many years and to Robert and Grunfeld may 
be given the honor of suggesting a method of biologically deter- 
mining- the activity of this drug. The method is that of producing 
the characteristic bluing or gangrene of the cock's comb and in 
1898 Houghton applied such a method commercially. In this 
method the drug is fed or injected intramuscularly into roosters, 
in such a dose as to cause bluing of the comb and I believe in all 
cases comparing the intensity of this action with some standard 
preparation. 

A second method is that of estimating- the amount of rise in 
blood pressure as a result of a given dose. The stronger the 
preparation, the higher the blood pressure in direct proportion. 
A third method is that of using the uterus itself as a test object, 
some workers carrying on the experiments on the intact animal 
and others on the organ isolated from the body. Usually cats 
are used, but dogs, guinea pigs, and rabbits have been tried, with 
less satisfactory results, however. The drug to be tested must 
be compared with a standard preparation carrying out the test 
upon the same organ since different uteri react very differently. 

Recently also Dr. Wood has suggested a chemical method based 
on the estimation of the benzole extractive, probably an impure 
ergotoxin, after precipitating the ergot with water. The increase 
in the amount of extractive was found by him to increase pro- 
portionally as the increase in blood pressure on injection of 
the drug in dogs. His premise is that blood pressure estimations 
are a true index of the activity of a given preparation and hence 
concludes that the benzole extractive is an accurate index of the 
drugs therapeutic properties. 

A further chemical method is the estimation of the Cornutine 
content of ergot — cornutine being an impure mixture of ergotixine 
and ergotinine. 

Dr. Edmunds of the University of Michigan and T have 1)een- 
engaged in a study of the assay processes for this druo-. Th^ 
investigation is not yet quite completed but both of us feel that 
cert'^in facts are fairly well established. 

The chemical methods of Dr. Wood and Professor Keller were 
used. In all cases duplicate and in certain instances quadruple 
estimations were made of both the cornutine content and the 
benzole extractive. Rippetoe's modification of Wood's method, 



"^^^kSch'mr™'} Biological Standardization of Drugs. 109 

that of taking an aliquot part, was also tested and gave results 
corresponding closely. 

The three biological methods were also employed. Cocks of the 
Leghorn variety and of nearly pure blood were chosen for ob- 
servations on the cock's comb. Mongrel roosters cannot be suc- 
cessfully used on account of individual variation. We have also 
some evidence that they should be of the same age, the older 
roosters apparently being more resistant. The drug was injected 
into the breast muscle as a rule but in a few instances into the 
thigh. The doses ranged from i to 4 c.c. of the fluid extract and 
in each instance a control rooster was injected with one of the 
preparations which we used as a standard. A minimal bluing 
was regarded by us as the best for making the comparisons but 
doses above and below this were given to insure greater accuracy 
of results. In this way difl:"erences of probably 15 per cent, could 
be determined. 

In the blood pressure work dogs anaesthetized with morphine 
were used and the drug in the dosage recommended by Wood was 
injected into the saphenous vein. The average of the maximum 
rise, the 5 minute and the 10 minute rise in blood pressure were 
^ taken as the index of the drugs activity. 

In the uterus method cats were employed for all determinative 
readings. For the intact animal, after anaesthesia, using chloral 
and ethyl carbamate, the animal was submerged in a large tank 
filled with salt solution to protect the uterus from the air. The 
abdomen was opened and a lever attached to the uterus. The drug 
was injected through a cannula into a vein. A standard drug as a 
basis of comparison was injected alternately with the ergot prepara- 
tion under consideration and the effect on the uterus recorded by 
the lever on a smoked paper. 

The work on the isolated uterus is much simpler. The animal 
is either killed outright or anaesthetized and the uterus removed. 
Only a very short section of this organ is used — in the contracted 
state not over a centimetre in length ; this is put in a small con- 
stant temperature bath which is filled with an oxygenated physio- 
logical salt solution after the formula of Locke. The organ is 
then attached to a writing lever in order to secure a record of 
its movements. 

Uterus tracings from different animals differ widely in char- 
acter which makes the effect of ergot difficult to read. After some 



no Biological Standardization of Drugs. {^'^ix^^^l;^\lu"'' 

experience, however, and after securing a large number of readings, 
all of which may be made on the same organ, a fairly definite 
idea may be obtained of the strength of the drugs, the standard 
and the unknown. 

As a result of these studies we have arrived at certain con- 
clusions basing them on the comparative values obtained from 
assays of a number of commercial preparations using the five 
methods outlined above. 

The three biological methods showed a very fair agreement 
while the results from the uterus and cock's comb methods showed 
an extraordinary one. This was a matter of considerable surprise 
to us since we had believed from a rather limited experience 
that the cock's comb method would not give concordant results. 
In this series there appeared to be an almost exact parallelism 
between these two methods throughout the series. The blood 
pressure method was generally concordant but in certain instances 
showed a wide variation from the results by the other methods. 

The two chemical methods did not show any definite relation 
to the biological methods although there was some agreement. 
The cornutine of Keller more closely paralleled the biological 
tests than did the benzole extractive of Wood, only three of the 
latter estimations in ii experiments corresponding to the rise in 
blood pressure. 

Just how closely the therapeutic value of ergot corresponds to 
the activity as expressed by these assays cannot be definitely deter- 
mined because of the complexity of the chemical substances found 
in this drug and also because of the variability in their actions. 
There is sufiicient evidence to show, even if the relation is not 
an exact one, that there is a fairly close correspondence, however, 
as is evidenced by the surprising agreement between the results 
by various biological methods. I am also convinced as with 
digitalis that the adoption of any one of these methods will result 
in the production of infinitely more uniform preparations of ergot 
than can now be obtained. The limits of variation from a given 
standard, as a definite amount of ergotoxine, would probably need 
to be fairly wide, but even with a standard allowing of consider- 
able variation a great deal would be gained for obstetrical patients 
who, as matters now stand, often gain nothing from the administra- 
tion of this important drug because of its inactivity. 

I stated in the beginning as an ideal that we should aim for 



Am. Jour. Pliarm. ) 
March, 1911. J 



Surgeons Grit Soap. 



Ill 



absolutely accuracy in all matters relating to drugs and this can 
only be secured through official recognition of some standard and 
a method of assay. Where accuracy of assay cannot be absolute 
it certainly is no unworthy ideal to ask in behalf of the sick for 
relative accuracy and uniformity such as biological assays and 
standards will give and I hope that it is not too visionary to think 
that biological methods at least for the digitalis group, for ergot 
and for suprarenal gland preparations may be adopted by the 
Pharmacopoeial revision committee. 



SURGEONS GRIT SOAP. 

By John K. Thum, Ph.G. 
Pharmacist at the German Hospital, Philadelphia. 

The thorough cleansing of the surgeon's hands previous to a 
surgical operation is of the utmost importance. Vigorous rubbing 
with soap and hot water, and plenty of it, is the usual initial perform- 
ance in sterilizing the hands of the operator. 

Lately, in place of the ordinary hard, soft, or liquid soap, some 
surgeons are using a grit or pumice soap. For reasons that are 
obvious, all dirt and foreign matter adhering to the hands are more 
easily and readily removed. 

For some reason the manufacturers of these pumice soaps make 
them exceedingly alkaline. As can be easily imagined this excess of 
free alkali is very prone to destroy the epidermis and render the 
hands of the surgeon sore and unsightly. For this reason the 
surgeon at the institution with which I am connected has ceased to 
use the commercial pumice soap and instead is using one of our own 
mianufacture. 

This soap was made by boiling cottonseed oil with strong solution 
of sodium hydroxide for one-half hour, adding a small quantity of 
alcohol to facilitate saponification, and precipitating the soap with 
a 20 per cent, solution of common salt. Common salt not only 
separates the soap but it also rids it of nearly all free alkali. The 
mixture was then thrown on a strainer and allowed to drain. The 
precipitated soap was then washed with distilled water and ex- 
pressed. Powdered pumice was next added and thoroughly incor- 
porated. The soap was then put into a suitable mold and placed, 
well covered with gauze, in a cool dry room, to harden. 



112 



Surgeons Grit Soap. 



{Am. Jour. Pharni. 
March, 1911. 



This method had its disadvantages, however. It required from 
five to six weeks to become firm and hard enough for its intended 
use. It also was somewhat brittle. This, however, was overcome 
to some extent by using potassium hydroxide instead of the sodium 
hydroxide, but the length of time for hardening was not materially 
decreased. Of course, this could have been overcome by using 
animal fat or tallow, but it is not always practicable or possible 
to obtain this readily. 

It then occurred to the writer that stearic acid and cottonseed 
oil in equal proportions might produce a soap that would harden 
at once or in much less time than the method described above. 

Accordingly some experimentation was carried on with this fatty 
acid and cottonseed oil and the results were both encouraging and 
satisfactory. So much so in fact, that the following formula and 
method of procedure was finally decided upon as yielding the better 
product. 



Cottonseed oil 500 c.c. 

Stearic acid 500 Cms. 

Sodium hydroxide 150 Cms. 

Alcohol 150 c.c. 

20 per cent, solution sodium chloride q.s. 
Distilled water q.s. 

Powdered pumice 300 Gms. 



Heat the cottonseed oil and stearic acid until the acid is com- 
pletely dissolved. Then add the sodium hydroxide, dissolved in 
a litre of distilled water, and heat for 15 minutes with constant stir- 
ring. Next add the alcohol and stir until saponification is effected. 
This is noticed by the mixture becoming homogeneous in a few 
minutes. Then add one litre of a 20 per cent, solution of sodium 
chloride and stir vigorously. Allow to stand until the soap is hard- 
ened ; the alkaline liquid, which remains at the bottom of the con- 
tainer, is then drained out by punching a hole in the soapy mass on 
one side. It is then washed two or three times with distilled water, 
melted, and while still on the fire, the powdered pumice is added, 
and the whole thoroughly incorporated. While still hot it is poured 
into suitable moulds. In twenty-four hours the soap is sufficiently 
hard enough for use. 



Am. Jour. Pharm.) 
March, 1911. / 



Standard for Caramel. 



113 



A STANDARD FOR TINCTURE OF CARAMEL.* 

By Geo. A. Menge. 

The subcommittee - in charge of color standards to be in- 
corporated in the new National Formulary has under consideration 
two methods for the color standardization of tincture of caramel ; 
by comparing it, or a given dilution with water, with a solution 
having a readily reproduced color value. The first of the methods 
proposed provides for a comparatively dilute solution, prepared as 
follows : 

Place 0.5 Gm. sugar in dry test tube 20 mm. diameter. Im- 
merse the tube to a depth of 5 cm. in a sulphuric acid bath, 
previously heated to 210° C. and keep at that temperature for 20 
minutes. Remove the tube and when cold dissolve in sufficient 
water to make 200 c.c. Add 50 c.c. alcohol and sufficient water to 
make exactly 250 c.c." 

A modification of this method has been suggested by Mr. 
Raubenheimer to the extent of substituting a bath of petrolatum at 
200° C. for the sulphuric acid at 210° C. 

The second method now in the hands of the subcommittee as 
modified by Mr. Raubenheimer, reads as follows : 

" On a sand bath heat 100 gm. of sugar to 200° C. and keep at 
that temperature for one hour, stirring constantly — then add suffi- 
cient water to make 100 c.c. when cold." 

From the point of view of the pharmacist the first method seems 
to me to be practically impossible. It obviously could not, with 
reason or common-sense, be applied without the advantage in equip- 
ment of a very effective enclosed hood — and such an advantage, 
I take it, is not common. To apply it without such equipment 
would entail great discomfort, if not more serious consequences. The 
fumes of sulphuric acid at 210° C. are abundant and more or less 
destructive, and their effect upon fixtures, upon pharmacists, and 

* Read at the meeting of the City of Washington Branch, Am. Pharm 
Ass'n., held February 11, 1911. 



114 



Standard for Caramel. 



iAm. Jour. Pharm. 
March, 1911. 



Upon any customers that might be at hand may reasonably be de- 
scribed as intolerable if, by any possibility, avoidable. 

Furthermore, the size of the vessel and the volume of acid 
required for the application of this method is quite considerable — 
sooner or later a beaker or other container would break, and 
sulphuric acid at 210° C, splashing around on fixtures and operator 
is another unpleasant possibility, associated v^ith this method. 

The suggested substitution of petrolatum for sulphuric acid 
seems to me to only change the character of danger and discomfort 
without greatly reducing either. 

The second method, while doubtless safe, would seem^ to be 
barely less objectionable in the detail of fuming. To heat 100 Gm. 
of sugar to 200° C. for i hour would surely caramelize the whole 
store — ^certainly the man who had to stand and stir for one hour 
would become thoroughly saturated with the odor of burnt sugar. 
Moreover the big time factor involved makes the method objection- 
able. 

In attempting to devise a more practical method than the two 
described above, I have conducted a series of experiments to deter- 
mine quantitatively the effect of sulphuric acid in direct contact 
with sugar as a means of producing colored solutions of the 
desired tint. 

Without taking time to describe experiments it is perhaps suffi- 
cient to say that I finally succeeded in obtaining a solution which 
conformed exactly, or very nearly so, to the color produced by the 
first method. 

The proceedure is as follows : 

Make a sulphuric acid solution by adding 2 c.c. of pure con- 
centrated sulphuric acid (specific gravity 1.84) to 12 c.c. of water. 
Take 0.5 Gm. of sugar in a test-tube — add 5 c.c. of the acid solution 
described above, and heat the mixture in a boiling water bath, with 
mixture continually submerged and with constant agitation, for ex- 
actly 5 minutes. Immediately add a little cold water and then 35 
c.c. of the U.S. P. test-solution of potassium hydroxide ; finally 
dilute to 100 c.c. 

The whole procedure takes 15 minutes, is absolutely with- 
out danger or discomfort, and gives correlating results that very 
closely approximate those obtained by the first method outlined. 



Am. Jour. Pharm. » 
March, 1911. j 



Automatic Water Still 



115 



AUTOMATIC WATER STILL. 



By F. J. Stokes. 



Several papers have been published in the American Journal 
OF Pharmacy on desirable forms of stills for pharmaceutical pur- 
poses. 

Professor Procter described a still for. apothecaries in the 
American Journal of Pharmacy for January, 1864, p. 12. This 
still was a modification of the apparatus described by him in 1848 
in the American edition of Mohr and Redwood's Pharmacy. In 
the same issue (page 22) Mr. Wiegand described a still which 
was primarily used to recover alcohol from various preparations. 



Somewhat later Neynaber (Amer. Jour. Pharm., 1865, p. 166} 
described an automatic pharmaceutical still in which a continuous 
distillation was affected. Pharmacists, generally, are familiar with 
the distillatory apparatus devised by Professor Remington (see this 
Journal, 1878, p. 15; 1879, P- 225). 

Without entering into a description of the various forms of 
stills which have already been devised, I shall consider a new and 
inexpensive automatic water still which is of interest to every 
druggist as it produces distilled water at the remarkably low cost 
of one cent per gallon per hour. It is gas heated and being- 
automatic requires no attention. It is fastened to the wall and 
gas and water connections can be made with rubber tubing. 




Ii6 Wholesale Druggists' /issoeiation. { ^" mi.''"' 

The main body and condenser of the stiU are cast in one piece 
which eliminates joints and makes it substantial. The dome or 
cover is porcelain lined to prevent corrosion while the condenser is 
block tin lined. The still is supported by a wall bracket from 
which it can be separated or slipped, without unscrewing, for the 
purpose of cleaning. 

The still consumes ten (lo) cubic feet of gas for each gallon 
of water distilled or at a cost of one cent per gallon. 

By a patented construction the Stokes Automatic Still accom- 
plishes two novel results. It utilizes the steam generated for heat- 
ing the feed water to the boiling point, so that a minimum of heat 
is required to operate it, and by this preliminary heating of the 
feed water the ammonia and other gases are largely eliminated. 

The following is a brief description of the still and its manner 
of action: The feed water enters at (H) in diagram, surrounding 
the condenser tube (C) and serves first to condense the steam 
generated in the still (B). As the steam descends the condenser 
tube it becomes heated to the boiling point by the time it reaches 
the top, where the ammonia and other gases escape into the air 
through the passage (F). A part of the feed water flows over 
the goose neck (E) into the sink and the balance passes into the 
still through the passage (M). The still is heated by a Bunsen 
burner. The distilled water comes out at (J) and can be piped to 
any receptacle. The condenser tube extends to the extreme top 
of the steam chamber and high above the water level, so there is 
no danger of water being carried over by the steam. 



THIRTY-SIXTH ANNUAL MEETING OF THE NATIONAL 
WHOLESALE DRUGGISTS' ASSOCIATION. 

By C. Mahlon Kline. 

The Thirty-Sixth Annual Meeting of the National Wholesale 
Druggists' Association was held at Dallas, Texas, and while the 
attendance naturally was less than if the meeting had been held at 
a more central location, the majority of those who have been active 
in the Association work in the past found time to attend. 

The meeting was characterized by the greatest harmony and 



^'MS;i9n'""'} Wholesale Druggists' Association. 117 

good feeling. Old ties of friendship were renewed, and had it not 
been for the discomforts afforded by the Southland Hotel, the meet- 
ing would have been in every way a memorable one. This hotel 
evidently calculated that the National Wholesale Druggists' Associa- 
tion would not be likely to meet again in Dallas for at least twenty 
years, and, therefore, proceeded in a cold-blooded way to make 
what it could out of its guests before they should escape from its 
clutches. One man upon being shown his room at the Hotel South- 
land, and finding it uninhabitable, decided to leave and go to another 
hotel. The management charged him for the day before and the 
day on which he rejected the room, before they would release his 
baggage. Such treatment is not calculated to make Dallas attrac- 
tive as a convention city, though in the past a number of conventions 
have held their meetings there. 

It is very difficult to separate from Texas the idea of a bound- 
less plain, unbroken by habitation, through which wild steers gallop 
unrestrained. As a matter of fact a wild steer could not gallop 
more than a few hundred yards before coming into contact with a 
modern up-to-date wire fence. The state is completely fenced from 
one end to the other, and is dotted over as far as the eye can see 
with innumerable farm-houses. There is very little of it that is not 
cultivated. The cotton fields are exceedingly fine, stretching for 
miles and miles over the level plains. The cotton plants them- 
selves appearing far more productive than those I have formerly 
seen in the south. According to the natives that I interviewed, 
this is correct, as the Texas cotton fields are said to produce about 
twice as much per acre as those in the South Atlantic States. For 
the accuracy of this statement I will not be responsible, as the aver- 
age native Texan is exceedingly proud of his state, and very boast- 
ful of what it can do. 

The meetings of the Convention were very ably presided over 
by the President, Mr. Chas. S. Martin, who made an unusually effi- 
cient presiding officer, and whose ability went far toward expedit- 
ing business and whose personality injected into the meetings an 
atmosphere of cordial geniality. It would be difficult to find a more 
able President than Mr. Martin has proven himself to be. 

The newly-elected President, Dr. Wm. J. Schieffelin. is well 
known to every one connected with the drug business in the United 
States to-dav, and his selection as President of the Association can- 
nf)t help but be approved by every one who has the pleasure of his 



Ii8 Wholesale Druggists' Association. {^'"MarXmr"' 

acquaintance. He can be trusted to look upon any matter in a 
broad, unselfish light, as he is animated by no petty thoughts of 
personal gain. It is such men as Dr. Schieffelin who help so much 
to make the National Wholesale Druggists' Association a broad 
power in the afifairs of the country at large, and an association which 
is known as seeking the public weal rather than its own selfish ends. 

Among those who addressed us at the first business session was 
Dr. Kebler of the Department of Agriculture at Washington. He 
spoke feelingly against the traffic in cocaine, morphine and opium, 
and also against those druggists who allow themselves to become 
mere " booze " sellers, stating that, in his opinion, the drug business 
should be absolutely divorced from the liquor business. Dr. Kebler 
made the statement that he believed over 80 per cent, of the morphine 
and cocaine sold in this country was used for illegitimate purposes, 
and that 1 per cent, of the people of the United States were habitual 
users of these drugs in one form or another. He said that he wanted 
to commend the action of Philadelphia druggists in refusing to sell 
certain commodities excepting on physicians' prescriptions, and also 
the National Association of Retail Druggists in putting themselves 
on record to the effect that they would use every possible effort 
to enact legislation which would tend to the eradication of those 
products that are sold indiscriminately to the public, containing 
cocaine, morphine, opium, etc. 

Prof. Eberle, President of the American Pharmaceutical Associa- 
tion, made a very interesting address before the Convention. Among 
other things, he said that he believed some means could be devised 
whereby closer association could be established between the A. Ph. A., 
N.A.R.D., and N.W.D.A., if in no other way than by having a 
counsel to which delegates from the three associations could be 
elected. 

Mr. Plant, in replying to Professor Eberle's remarks, paid a very 
high tribute to the American Pharmaceutical Association and to the 
excellent scientific work that was effected by the Bulletin of this 
Association. In alluding to the encouragement which should be 
given to the American Pharmaceutical Association in its work, Mr. 
Plaut said that a man of education and of culture, who is efficient 
and proficient in his profession, is a better customer, pays his bills 
more promptly, is a more pleasant person to meet, than the mere 
seller of ready-made medicines. Mr. Plaut also stated that the 
American Pharmaceutical Association stood very high in Con- 



^'"MaS';i9iL'""} Wholesale Druggists' Association. 119 

tinental Europe, that its prominent members are well known, its high 
standing is recognized, and every American who visits foreign 
pharmacists and foreign laboratories will be surprised to know 
that very frequently these gentlemen are better known in foreign 
countries than they are among ourselves. Mr. Plant urged every 
one to join the American Pharmaceutical Association, and thus assist 
in the elevation of pharmacy. 

President Martin in his presidential address touched upon many 
topics of importance to the country at large, which I shall not attempt 
to repeat, and which are really not capable of being condensed, as 
they would necessarily have to be, to be included in this paper. 
Sufficient is it to say that his report showed that the Association 
has co-operated with many commercial bodies throughout the coun- 
try and assisted in bringing about important improvements in trade 
conditions. Mr. Martin advised that the authorities on legislation 
be instructed to support the passage of an amendment to the Food 
and Drug Act, adopting the use of the name Wood Naptha " 
to take the place of the name " Wood Alcohol," which name is 
misleading and has often caused death and blindness because of 
misunderstanding as to the character of the substance. President 
Martin called the attention of the Association to the fact that the 
world has reached that stage in its progress when little is accom- 
plished except through organization and united effort, and that the 
day of small things has passed and it is the duty of all to participate 
in the organized effort that makes for the good of the whole. 
He stated that it was not fair, in fact, it was a gross wrong, that 
the burden of organization be left on the shoulders of the most 
enterprising and conscientious, while the selfish, the indolent, and 
those without a proper scruple in appropriating the fruit of other 
people's labor, remain at home. 

The report of the Committee on The Prevention of Adulteration 
was exceedingly interesting this year, and all those interested in 
scientific study and the purity of drugs, as they are offered on the 
markets, should read the report in full. The Committee stated that 
an eminent expert, who not very long ago uttered in the public 
prints a rather wholesale denunciation of the traffic in crude drugs 
on the ground of widespread practices of sophistication, has more 
recently been quoted as saying that there is no longer one-tenth the 
adulteration there was formerly. The report then called attention 
to the indiscriminate looseness with which the words adulteration " 



I20 Wholesale Dnig-gists' Association. { ^""naX mi."""* 

and " adulterated are used. These words are employed daily in 
official utterance, rendered in a way which has robbed them of their 
original significance. The deliberately corrupted product of the 
fraud and the cheat when discovered is called "adulterated," and the 
innocent material which, although absolutely unsophisticated and 
intrinsically of the highest merit, happens to exhibit some slight 
defect in respect of a rigidly fixed standard, is condemned by ex- 
actly the same formula ; it is " adulterated." The element of moral 
turpitude appears to have been eliminated and must no longer, with- 
out proof, be assumed to be present where cases of adulteration are 
reported. At a later meeting the Association took action on this 
condition as follows : Resolved, That the incoming Committee on 
Legislation be instructed to take such steps as will bring about, at an 
early date, the abolishment of the improper use of the words adul- 
teration " and " adulterated " in the publications of the Board of 
Food and Drug Inspection, as mentioned at length in the Com- 
mittee's report. In this connection Mr. Plant brought up a point 
which is very important : he called the attention of the Association 
to the fact that the inspection to which goods are subjected at the 
various points of entry are anything but uniform. He mentioned 
a case where asafetida bought in Hamburg and sold to a house in 
Philadelphia was entered at the port of Cleveland, and -stated that 
other drugs were being entered at such points as Minneapolis, 
Cleveland, Ogdensburg, Albany, etc., where there were no thor- 
oughly organized Bureaus, equipped to test the quality of the 
drugs, and that in this way inferior drugs obtained admission to 
the country in a way that could not be effected were they entered 
at some of the regular ports of entry. He advised that the mem- 
bers use their efiforts to abolish this objectionable condition of 
afifairs. Mr. Plant also brought to the attention of the Association 
the present method of printing the court decisions in the case of 
prosecutions brought by the Department of Agriculture. As they 
are printed they are sent broadcast over the country, and it is 
necessary often to read the leaflet from beginning to end before the 
reader finds out whether the defendant is innocent or guilty. Many 
people read but the first few lines and are left with a false impres- 
sion that the defendant has committed a crime, whereas often the 
last few lines would prove that he was absolutely innocent. Many 
delegates recognized the truth of this contention, and a resolution 
was passed requesting the Committee on Legislation to look into the 



^%l?ch:mi™'} Wholesale Druggists' Association. 121 

possibility of having the decisions in which the defendant is not 
proven guilty published in a form different from that in cases in 
which he is convicted, or else that no notice be issued in such a case. 
To return to the report of the Committee on the Prevention of Adul- 
teration, the report also contends that under the operation of the 
law, dealers are purchasing goods under a U.S. P. label for resale, 
even though they know, or suspect that such goods are not what 
they exactly seem to be, and that they smother their true beliefs 
by the expression, " What is it to me what the bottle actually con- 
tains, does it not bear the guaranty of a reliable house?" The 
Committee contends that the purchasing departments can do much 
to prevent adulteration by curbing this insidious tendency. The 
Committee believes that the work of the Government inspectors em- 
ployed in inspecting the quality of important drugs has undoubtedly 
become more and more effective. There is still, however, they be- 
lieve, a great deal of inconsistency in the methods employed and too 
strong a tendency to be over-technical in the application of the law 
to cases where there is obviously no sophistication or demerit. It 
will be necessary for me to pass over the details of the balance of 
the report, because they are many and would take too long to read 
at this time. 

The report of the Committee on Trade-marks contained much 
of interest. The case of the manufacturers of the " Keep Clean 
Brushes " against the manufacturers of the " Stay Clean Brushes " 
was cited, in which it was found that, though neither word was 
capable of being trade-marked, because a descriptive word cannot 
be trade-marked under our present law, nevertheless, under the laws 
of unfair competition, the manufacturers of " Keep Clean Brushes " 
were enabled to obtain a judgment against the manufacturer of 
" Stay Clean Brushes,'' because (I quote from the decision) " Where 
the defendant has so dressed his goods that they may be mistaken 
for the goods of the complainant, his motive in so doing is either 
honest or dishonest; if honest, he should stop voluntarily, if dis- 
honest, he should be compelled to stop." The Committee called 
attention to the Trade-mark Law in California, under the terms 
of which the manufacturer, in order to protect his rights within the 
state, must register his trade-mark with the state authorities. A 
test case is being brought to prove this law unconstitutional, but in 
the meantime the manufacturers are advised to register their trade- 
marks in order to fully protect their rights. 



122 Wholesale Drup-g-ists' Association. |Am jour. Pharm. 

I March, IWl. 

The Committee on Paint, Oils and Glass, the advisability of con- 
tinuing which had been questioned the previous year, proved its 
worth by coming forward with an excellent report, including many 
points of undoubted interest and value. The Hepburn Paint Bill 
was discussed, but what will interest this meeting more was that 
part of the report of the Committee which has to do with turpentine. 
Under the Pure Food and Drugs Act it would be necessary for tur- 
pentine, or spirits of turpentine, to be unadulterated and to answer 
the U.S. P. requirements, or else to be properly labelled. Under the 
ruling whereby an article of this character can be labelled " For 
technical use " the dealers are enabled to sell an adulterated product 
without fear of prosecution. Hiding behind this regulation, a large 
traffic in adulterated turpentine has been carried on, and no dealer 
to-day can be absolutely sure he is dispensing pure spirits unless he 
either tests the goods himself, or knows personally that the dealer 
from whom he buys is absolutely honest. There are three common 
adulterants : First of all, spirits of turpentine is distilled from the 
dip or scrape of the living pine tree. The first adulterant, pure wood 
spirits of turpentine, is made by the destructive distillation of the 
wood; another adulterant is common benzine; still a third is com- 
posed of high boiling hydrocarbons analogous to benzine. Pure 
wood spirits naturally forms an excellent adulterant, due to the 
fact that it is very similar in physical properties. Common benzine 
is the poorest adulterant, on account of its odor and physical prop- 
erties. The high boiling hydrocarbons, being odorless and very 
similar to turpentine in physical properties, make an ideal adulterant. 
Twenty-three samples, most of them obtained from suspected 
sources, were analyzed by the Committee. Out of the 23 tested, 
17 showed adulteration; the average amount of adulterants being 
30 per cent. The greatest amount of adulteration was found in Rus- 
sian turpentine, which contained no trace of turpentine at all, being 
petroleum. The lowest amount was 10 per cent., this being the 
percentage usually put in by several unscrupulous dealers in New 
York City, who sell their product as " pure spirits of turpentine." 
The quotations of these dealers are always a cent or two under the 
Official Naval Stores prices. Another group of turpentine adulter- 
ators, using about 35 per cent, petroleum, made their headquarters 
in Cleveland, Ohio. One firm is quite clever, guaranteeing their 
product to be " pure " according to the analysis printed on the head 
of the barrel, and not stating whether it was pure turpentine or pure 



^""mS; fm""' } IVholesale Druggists' Association. 123 

benzine. The State of Ohio recently passed a Pure Turpentine 
and Linseed Oil Act which has caused much annoyance to the 
dealers in adulterated products in that state. The Committee rec- 
ommends the enactment by each state of a similar law. I made a 
study of this law, which at first seemed very drastic, but on further 
consideration, every detail can be lived up to by an honest man doing 
an honest business and will work no hardship on any one who comes 
under this heading. The law states that no one shall sell under 
the name of turpentine, or spirits of turpentine, or any compounding 
of the word " turpentine,'' or under any name or device illustrating 
or suggesting turpentine or spirits of turpentine, any article which 
is not wholly distilled from rosin, turpentine, gum, etc., and unmixed 
and unadulterated with oil, benzine, or any other foreign substances 
of any kind whatsoever, unless the package be marked with letters 
not less than 2 inches high, Adulterated Spirits of Turpentine." 
It can be readily seen that this law covers the situation nicely, and 
Pennsylvania would do well to adopt such a law, and I recommend 
that you, whenever the opportunity presents itself, speak a word in 
favor of such legislation. I would be glad to supply any number 
of copies of the Ohio law to those who would like to study it. 
The Chairman of the above-mentioned committee, Mr. Levi Wilcox, 
of Waterbury, Conn., deserves high commendation for his very 
excellent report. 

The report of the Proprietary Committee, of which Dr. Schief- 
felin was Chairman, contained considerable of interest to the trade. 
The general tendency, the Committee reported, of decisions rendered 
by various courts throughout the land, was to take a less drastic 
position with reference to the violation of the Sherman Anti-Trust 
Law. Two cases were referred to in this country and one in Canada 
where the court took the position that the manufacturer had the right 
to insist upon the maintenance of his retail price where it could be 
shown that such an action is only incidentally and indirectly to resist 
competition, while its chief result is to foster the trade and increase 
the business of those who make and operate it. These decisions, 
so different from the one rendered at Indianapolis in the case of the 
United States against the drug trade, tend to increase confidence 
in the stability of business and encourage manufacturers to spend 
larger amounts in advertising their goods, because they feel that 
they can protect their interests by being allowed to maintain their 
price to the consumer. An important decision was cited which 



124 Wholesale Druggists' Association. {^^f?"" im"""" 

increases the value of the guarantee, and shows that the courts will 
accept a chain of guarantees as fixing the blame on the original 
guarantor, and that he will be held responsible for fraud even though 
technicalities may be brought to bear on the case. The case in ques- 
tion is one in which a manufacturer sold to a wholesaler in the 
same state and the wholesaler in turn sold to a retailer in a nearby 
state. The manufacturer attempted to evade responsibility on the 
ground that his sale was only one within the state, rather than an 
interstate sale, but the courts decided otherwise. The report calls 
attention to the National Insecticide Act, which was intended to go 
into effect on January ist, 191 1, and with which you are probably 
familiar; if not, you had better send for a copy of the Act, as its 
provisions are more inclusive than you would at first think. The 
definition is exceedingly broad, and covers insect powders, powdered 
white hellebore, and every drug or preparation, proprietary or other- 
wise, which is intended to exterminate insects of all kinds. It also 
includes fungicides. A committee was appointed by the three 
secretaries to formulate regulations for the enforcement of the Act, 
which committee has not yet reported the nature of these regulations, 
therefore, all dealers have been obliged to hold up the printing of 
their labels until such regulations are promulgated, because other- 
wise it might be necessary for them to make two changes in order 
to comply with the law. Dr. Schieffelin commented on the Owens' 
Bill, which provides for the establishing of a National Department 
or Bureau of Health. He stated that his committee opposed that 
portion of the bill which gives the proposed department power to 
establish standards for chemicals and other drugs, because they 
took the position that this was unnecessary, as the present arrange- 
ment, which makes the United States Pharmacopoeia and National 
Formulary the official standard, is sufficient. There is no question 
that the National Department or Bureau of Health could utilize the 
vast resources of the Federal Government to the great advantage of 
the nation, by gathering and disseminating information, and materi- 
ally assisting in preventing diseases and preserving the health of 
the people. He believes this could be done without encroaching 
upon the constitutional prerogative of states to exercise police power 
within their respective borders. The health of our people is the 
greatest asset of the nation, and any feasible plan that will minimize 
the loss of valuable human lives is worthy of the most careful con- 
sideration. 



^'"mSiqu^""} Wholesale Druggists' Association. 12^ 

The report of the Committee on Legislation, whose Chairman is 
Mr. Chas. A. West, of Boston, shows that they have done much 
valuable work during this period when it seems to be every politi- 
cian's ambition to invent some new provision whereby the drug trade 
can be better controlled. The work of this committee is exceedingly 
arduous, and it would be practically impossible for the Chairman to 
operate effectively in every state in the Union, were it not for the 
fact that the individual members in the states themselves willingly 
furnish their co-operation. One of the bills mentioned by this com- 
mittee that is now before congress, was introduced by Mr. Moore 
of Pennsylvania. It provides for the labelling of packages contain- 
ing foods, beverages, and drugs, and makes it necessary that they 
should show the weight or measure on the label. That such a 
requirement should be made in the case of drugs, whose value does 
not depend by any means on their weight or measure, is manifestly 
ridiculous, and the bill has been opposed by the committee. It 
seems likely that in its present form it will not be passed, but that 
it will be revised and be made more comprehensive, because as at 
present worded it only covers the District of Columbia. As the bill is 
at variance with several state laws pertaining to weights and meas- 
ures, if passed, it will cause a great deal of confusion. The Com- 
mittee calls the attention of the Association to the fact that the 
Pure Food and Drugs Acts passed in the various states are very 
similar. The attempt to carry out the law by making rules and regu- 
lations has proven rather disastrous. The individual who is given 
the power to make such rules and regulations often largely exceeds 
his authority, or else insists upon minor points of detail, which, be- 
cause they differ in the different states, make interstate transactions 
exceedingly difficult. A label which will comply with the National 
Law often will not comply with the state regulations, and if it does 
comply with the regulations of that state, will not comply with the 
regulations of other states. It must be remembered that the law is a 
law to prevent adulteration and misbranding only, and that the final 
word as to whether goods are mislabelled or not is to be decided 
on those two points only. The Committee requests that the mem- 
bers attempt, as far as possible, to counteract this tendency toward 
the issuing of annoying regulations, and, in the opinion of the com- 
mittee, this matter requires some positive action on the part of the 
united drug interests. 

The Legislative Committee reports much activity along the line 



126 Wholesale Druggists' Association. {^"mSX um'"' 

of narcotic legislation. This seems to have become a favorite sub- 
ject for new bills. Three important ones are now under considera- 
tion; the Mann Bill, the Collum Bill, and the Foster Bill. The 
Mann Bill requires that all sellers and shippers of habit-forming- 
drugs shall keep an exact record, regardless of what the shipment 
may be, and requires a record of such shipment to be kept by the 
receiver. A number of minor points in the bill seem calculated to 
work injustice, and the committee, therefore, considers that this Bill 
should be revised before it receives the support of the drug trade. 
The Collum Bill was introduced in the Senate, but being a revenue 
measure, was rejected, as such legislation could only originate in the 
House. The Foster Bill purposes to place the control of the traffic 
in narcotic drugs in the charge of the Internal Revenue Department. 
In order to accomplish this purpose it provides that every wholesale 
dealer and retail dealer shall be registered, and no sale shall be 
made excepting to those who have been properly registered. A fine 
of $500 or imprisonment for one year is the penalty for shipping to 
any one not properly registered. It also provided for an Internal 
Revenue tax of 5 cents a pound or fraction of a pound on opium, 
chloral, and cannabis, and i cent a pound on coca leaves. A num- 
ber of methods of keeping the accounts are provided. The plan 
to carry out the Internal Revenue control is to put on a stamp, 
sealing the package, before it is released from a bonded warehouse. 
The general attitude of the committee is that this measure would be 
exceedingly burdensome and that it might be possible to accomplish 
the result in some way less burdensome. Mr. Hamilton Wright, the 
United States Opium Commissioner, pledged himself to the passage 
of some bill regulating the traffic in opium, when he was a delegate 
to the International Opium Congress. He, therefore, considers 
that, in order to keep faith with the Congress, it is exceedingly 
desirable that some legislation should be passed in the near future. 
He is somewhat in favor of the Foster Bill, but not definitely com- 
mitted to its passage. The representatives of the N.W.D.A. have 
attempted to persuade him that if this measure should be passed it 
should be made applicable to cocaine alone at first, until the measure 
is tried out. This suggestion Mr. Wright has under consideration. 
There is 400,000 lbs. of opium imported into the United States in a 
year. Of this it is estimated 300,000 lbs. is used for purposes other 
than medicine. This figure is very high as compared with the 
amount consumed in other countries where they have effective laws 



Am, Jour. Pharm. J 

March, 1911. f 



Progress in Pharmacy. 



127 



governing the traffic in narcotic drugs. The Committee reports that 
in the case of the Pure Food & Drugs Act it is pretty generally 
acknowledged by those most familiar with the workings of the law, 
even including officials, that the labelling clauses are rapidly losing- 
effectiveness, especially so far as the public is concerned. The public 
does not read the labels or does not understand what it does read. 
This opinion is so generally accepted that there are many who hope 
for the enactment of laws that will compel the manufacturers to put 
in his advertisements all that the law compels him to put on his label. 

One thing more I think worth mentioning : the following resolu- 
tion was passed by the Association : Whereas, The attention of the 
N.W.D.A. has been called to the fact that efforts are now being 
made to change the form, style, and spelling of the articles used as 
drugs and chemicals in the coming revision of the U.S. P., be it there- 
fore. Resolved, That this Association protests against any changes 
in form, style, and spelling, except those which may be necessary 
in the few cases where more exact information and research requires 
a change. The resolution was introduced because the Association 
was informed that certain parties were bringing pressure to bear 
to have the form, style, and spelling of the Pharmacopoeia changed. 
It requires no argument to prove to you what a mistake this 
would be. 

In closing, I would say, that the meeting at Dallas was an entire 
success, and the members of the Association expect to spend at least 
another year working in perfect accord toward the betterment of 
conditions in the drug trade without any factional quarrels to mar 
the effectiveness of their work. 



PROGRESS IN PHARMACY. 

A QUARTERLY REVIEW OF SOME OF THE MORE INTERESTING LITERA- 
TURE RELATING TO PHARMACY AND MATERIA MEDICA. 

By M. I. WiLBERT, Washington, D. C. 

Few subjects, now before the retail druggists of this country, 
have received more widespread attention by the pharmaceutical 
press than the Foster anti-narcotic bill which is being considered by 
the Ways and Means Committee of the House of Representatives. 



128 



Progress in Pharmacy. 



/Am. Jour. Pbarm. 
\ March, 1911. 



This bill is practically a duplicate of the Cullom bill which was 
considered in the Senate last year, and as now worded is designed 
to regulate traffic in cocaine and other habit-forming drugs by 
imposing an internal revenue tax and requiring that detailed records 
of all sales be made and reported to the Commissioner of Internal 
Revenue who is also to make regulations for the enforcement of 
the act. 

In the hearings that have been held on this bill it was generally 
admitted that the abuse of habit-forming drugs had spread to an 
alarming extent, in the last 20 or 30 years, and that their con- 
sumption, at the present time, was not accounted for by any 
legitimate use to which they could be put. 

It is also agreed that the only way by which the several State 
laws regulating the sale of habit-forming drugs could be enforced 
was by having an authoritative source of information regarding the 
sale, in a large way, of the several articles that are involved. 

It must be admitted that this law, or any law of a similar nature, 
will entail hardships and will involve the expenditure of time and 
money on the part of those engaged in the several branches of the 
drug business. But, on the other hand, the possibility of removing 
from the drug trade the stigma of debasing all strata of society 
by the encouragement of drug habits is one that should and no 
doubt will atone for all the trouble and expense that can possibly 
be involved. 

Public Health Service. — Legislation looking toward the pro- 
tection of the public health has also been discussed at length and 
some progress has been made toward the solution of the problems 
involved. The report of the Committee on Interstate and Foreign 
Commerce, indorsing the Mann bill, to change the name of the 
Public Health and Marine-Hospital Service to the Public Health 
Service and defining its field of usefulness, is reprinted in the Oil 
and Paint Reporter (February 6, 1911, p. 40) and pharmacists who 
are interested in the progress of public health legislation should 
read this report and consider the possibilities involved. 

Ph. Germ. V. — In Europe the new ^'Deutsches Arzneibuch " 
has been probably the most fruitful topic of discussion. This book 
while much larger than any of its predecessors contains but a total 
of 43 more titles than the Ph. Germ. IV. It represents a rather 
radical change in the method of revision in that it is the direct 
product of the " Reichs Gesundheitsamt," being compiled by the 



Ana. Jour. Pharm. ) 
March, 1911. / 



Progress in Pharmacy. 



i2g 



division on materia medica. This division consists of two sub- 
divisions, one medical and one pharmaceutical, and the work on the 
pharmacopoeia represents the contributions of 26 experts. 

An editorial {Pharm. Zentralh., 1910, v. 51, pp. 1177-1179) 
points out that the new Ph. Germ, has a decidedly broader field of 
usefulness than its predecessor and that the concise and altogether 
limited descriptions of the former editions have been replaced by 
more complete monographs, which will be found to be of value not 
alone in the pharmaceutical laboratory but also in the use of the book 
by students and by physicians who will find in them much infor- 
mation of practical value. 

The general formulas were increased by 13, viz., bacilli, cerata 
chartae, coUemplastra, mucilagines, pastse, pulveres, mixti, sapones 
medicati and vina medicata. 

The provisions of the Brussels protocol have been adopted with 
the special designation P. 1. 

With the titles adeps suillus, sebum ovile, spiritus e vino and 
vinum no descriptions or tests are appended, and these articles are 
expected to conform to the requirements made for commercial 
articles. 

Trademark Names. — A review of the new German Pharmaco- 
poeia points out that the repeated occurrence of protected designa- 
tions in the list of additions will surprise those who have followed 
even superficially the recent trend of events in Germany. It has 
been the aim of the responsible authorities so far to avoid in any way 
recognition of vested rights, and thus in the last edition the German 
pharmacist was regaled with the appalling scientific appellations for 
antipyrin and salipyrin. In the draft of the present edition, this 
attitude was adhered to, and the full chemical designation of novo- 
caine and stovaine, for instance, figured as the only titles to the 
respective monographs. The explanation of this vollte-face is not 
without interest and piquancy. We are told that where the scientific 
designation is more convenient or in general use it has been adopted ; 
in other cases the protected name was chosen for the title, followed 
by the chemical name and the protected name also appears beneath 
the scientific title as a subtitle. The adoption or mention of the 
registered appellation, however, merely indicates that the protected 
preparation must in every respect fulfil the requirements set forth 
in the Pharmacopoeia. — Chem. and Drug., Lond., 1910, v. 77, p. 899. 

Post-Graduate Instruction. — The Pharmaceutical Institute of 



I30 



Progress in Pharmacy, 



i Am. Jour. Phanu. 

\ Mairli, 1911. 



the University of Strassburg announces that a post-graduate course 
of instruction, covering the changes and requirements of the Ph. 
Germ. V., is now being arranged for. The course is designed as a 
review of the more important tests and assay methods of the pharma- 
copoeia and will consist of lectures, demonstrations and practical 
laboratory work. — /. d. Pharmacie v, Elsass-Lothringen, 191 1, v. 37, 
p. 292. 

British Pharmacopceia. — Edmund White, in resigning as a 
member of the British Pharmacopoeia Committee of Reference in 
Pharmacy expresses himself as being dissatisfied with the progress 
that is being made in revising the British Pharmacopoeia. He 
thinks conditions existing in connection with the revision of the 
British Pharmacopoeia are quite unsatisfactory and points out that the 
German Pharmacopoeia, which is now a State publication, has been 
developed along much more satisfactory lines. — Chem. & Drug., 
London, 191 1, v. 78, pp. 186-187. 

British Pharmaceutical Codex. — An editorial asserts that 
the revision of the British Pharmaceutical Codex is now well 
advanced, though it may be several months before it approaches 
completion. The editorial also points out that most gratifying re- 
sponses have been received from all to whom appeals for assistance 
have been made and the Codex as revised may therefore be depended 
upon as representing the consensus of opinion of practicing pharma- 
cists throughout Great Britain. — Pharm. J., London, 1911, v, 86, 
p, 2. 

The Codex Revision Committee is regularly publishing sug- 
gested new formulae and alterations with the request that they be 
reviewed by pharmacists and that criticisms and further sugges- 
tions be forwarded to the office of the committee. These published 
formulae have elicited considerable comment, and it is expected that 
the book as finally published will be free from the glaring errors 
usually found in works of this kind. 

International Congress of Applied Chemistry. — William 
H. Nichols (Science, 1910, v. 32, p. 689) discusses the origin and 
development of the International Congress of Applied Chemistry, 
and calls attention to the need for making active preparations for 
the eighth international Congress which is to meet in this country 
early in September of 1912. 

John Morgan. — A news note announces that at a meeting held 
in the office of the Provost of the University of Pennsylvania, on 



Am. Jour. Pharm. ) 

March, 1911.); / 



Progress in Pharmacy. 



January 13, it was decided to erect a suitable memorial to Dr. John 
Morgan, the founder of the medical department of the University, 
the originator of medical schools in the United States, and the first 
physician, in America, to introduce the writing of prescriptions. — 
/. Am. M. Ass., V. 56, p. 205. 

Paris School of Pharmacy. — Professor Guignard, who desires 
to devote himself hereafter solely to scientific work, has requested 
the minister of public instruction to relieve him of the directorship 
of the higher school of physiology and pharmacy, which he has 
carried on for about 15 years, having succeeded Professor Planchon. 
The faculty of the school has unanimously elected, as the new direc- 
tor, M. Henry Gautier, professor of inorganic chemistry at the 
school. — /. Am. M. Ass., 191 1, v. 56, p. 130. 

Medical Curriculum. — An editorial note {Chem. & Drug., 
Lond., 1910, V. 77, p. 834) quotes the Lancet which suggests that 
the reaction against studying materia medica in the medical cur- 
riculum has gone too far, and although it is hopeless to attempt to 
reintroduce the old materia medica a modified form should be 
tried, and outlines a course that might well be adopted in British 
medical schools. 

Progress in Pharmacology. — An editorial commenting on the 
programme of the Section on Pharmacology and Therapeutics of the 
British Medical Association asserts that pharmacists, if they are to 
keep up to date, must keep in close touch with that branch of medi- 
cine which deals with the study of the composition and uses of 
remedies of medicinal value and they must therefore know about the 
shifting of the old landmarks and note the progress which pharma- 
cologists make in elucidating the action of medicinal agents. — 
Chem. & Drug., Lond., 1910, v. 77, p. 832. 

Antityphoid Vaccination. — George B. Foster reports an in- 
stance illustrating the efiicacy of antityphoid vaccination in the 
U. S. Army. Of 92 members of Company A, First Battalion of En- 
gineers, who were vaccinated, not a single case of typhoid fever 
developed, while of the total of 24 men not so protected six, or 
25 per cent., developed typhoid fever. — /. Am. M. Ass., 1910, v. 55, 
pp. 1 808-1 809. 

Essential Oils as Antiseptics. — An editorial in discussing 
the use of essential oils as antiseptics points out that essential oils 
or substances containing them are the oldest antiseptics that have 
been used by man, but that it is only within recent years that any 



132 



Progress in Pharmacy, 



I Am. Jour. Pharm. 

I Maiilj, 1911. 



systematic study of their antiseptic action has been made, in a 
recent investigation made by W. H. Martindale to determine the 
carboHc acid coefficient of each oil or aromatic substance studied, it 
was found that oil of origanum had upwards of 25 times the co- 
efficient of carbolic acid ; thymol and carvacrol were found to be 
nearly as active as oil of organum, the coefficient figures being 25.29 
and 21.32 respectively. — Chem. & Drug., Lond., 1910, v. 77, p. 832. 

Chemistry of the Terpenes and Camphors. — Joseph Samuel 
Hepburn, in a recent number of the Journal of the Franklin Insti- 
tute (February, 1911, v. 171, pp. 179-203), presents an interesting- 
review of the work that has been done by Otto Wallach and his 
students on the chemistry of the terpenes and camphors and their 
related compounds. As many of the compounds referred to are 
official or at least common articles in the average drug store, this 
review will be found to be of unusual interest to pharmacists who 
are desirous of learning the relations existing between them. 

Stirring Rod. — An abstract (from Siidd. Apoth.-Ztg., 19 10, 
p. 622) points out that glass tubing properly sealed at either end 
makes a much better stirring rod than a soHd glass rod. The 
resulting rod is lighter, has a greater volume, and, as a rule, does 
not break so readily, even when dropped on a wooden table. — 
Schweiz. Wchnschr. f. Chem. u. Pharm., Zurich, 1910, v. 48, p. 765. 

Melting-Point Determination. — Atherton Seidell describes 
and illustrates a convenient arrangement for providing constant 
stirring of the sulphuric acid or other bath in making melting-point 
determinations. The mechanical stirring device is driven by a small 
water motor, while an even heating of the bath is insured by protect- 
ing the flame from air currents and by preventing the free flame 
from coming in contact with the tube containing the bath. — /. Am. 
Chem. Soc., 1911, v. 33, p. 83. 

Drops. — Wulff and Hillen describe and illustrate a normal drop 
ampoulle which they believe to be particularly well adapted to 
serve as the normal drop counter provided for by the Brussels Con- 
ference Protocol. 

The apparatus can be used for dispensing substances that are to 
be used in drop doses, particularly solutions to be used in the eye, 
where sterility is considered to be an important factor. — Apoth. 
Ztg., Berl., 1909, V. 25, p. 1014. See also Pharm. Post, 1911, v. 44, 
p. 53. 

Salvarsan is the name under which " 606 " is being marketed 



Am. Jour, Pharm. ) 
March, 1911. / 



Progress in Pharmacy. 



133 



in this country. A number of papers on the chemical and pharma- 
ceutical properties of this substance have appeared in the current 
journals and the information necessary for preparing the material 
for injection is available from the literature accompanying the 
package. 

A report on the chemical properties of salvarsan, by W. A. 
Puckner and W. S. Hilpert (/. Am. M. Ass., 191 1, v. 55, p. 2314), 
contains the following popular description of its behavior : " Sal- 
varsan is an arsenic compound containing that metal in a low state 
of oxidation and the product is, therefore, a powerful reducing 
agent and is decomposed by bodies which are oxidizers, including 
air. Being a weak base its hydrochloride, when dissolved in water, 
is largely decomposed by the latter (hydrolyzed) and hence gives a 
solution having an acid reaction. A solution of salvarsan is there- 
fore acid and will remain so until for every molecule of salvarsan 
there have been added two molecules of sodium hydroxide or a 
similar monovalent base." 

William Allen Pusey, in a discussion of the situation regarding 
salvarsan, asserts that indications are very strong that we are on the 
verge of a period of indiscriminate and reckless use of this remedy 
that will result in disappointment and damage to many patients. 
He further points out that this drug does not absolutely cure syphilis 
and that in the hands of careless or incompetent practitioners it is 
likely to do much harm. — /. Am. M. Ass., 191 1, v. 51, pp. 1 18-120. 

A recent number of N. A. R. D. Notes (February 2, 191 1, p. 
998), calls attention to an advertisement from the Chicago Sunday 
Examiner of January 23, 191 1, in which salvarsan ("606") is 
being indirectly exploited to the laity. Needless to say advertise- 
ments of this type are destined to do an untold amount of harm. 

JoHA is the name applied to an oil solution of salvarsan that 
is said by its promoters to be quite stable. It is being marketed in 
Germany, in ampoulles containing the equivalent of 0.4 and 1.2 
Gm. of salvarsan. — Pharm. Zentralh., 191 1, v. 52, p. 21. 

Adalin is the name given to brom-diethyl-acetyl urea. This 
substance occurs as a colorless, nearly tasteless powder that is only 
sparingly soluble in cold water but freely soluble in alcohol. Adalin 
is being recommended as a bromide and is given in doses of from 0.3 
to i.o Gm. three times a day. — Pharm. Post, 191 1, v. 44, p. 84. 

Am POT. is said to be a preparation of mineral fats that is per- 
manent and has the property of absorbing upwards of 30 per cent, 
of water. — Pharm. Zentralh., 191 1, v. 52, p. 52. 



134 



Progress in Pharmacy. 



( Am. Jour. Pharm. 

\ March, 1911. 



Adrenine. — Macadie, W., discusses the coloration of solutions 
of adrenine (adrenalin) and records a number of experiments made 
by him to prevent the development of free ammonia which he be- 
lieves is the causative factor. He has found chloroform to be the most 
efficient antiseptic and recommends keeping a layer of chloroform at 
the bottom of the solution of adrenine, which is to be kept in dark 
amber-colored bottles. — Pharm. J., Lond., 1910, v. 85, p. 660. 

Afridol. — An abstract asserts that afridol, which is recom- 
mended as a powerful antiseptic and disinfectant, is an ortho- 
toluate of mercury and sodium of the formula (CgHg) (CH3) (CO^ 
Na) (HgOH). It is especially recommended as a component of anti- 
septic soaps for disinfecting- the hands and instruments in the course 
of surgical operations. — Chem. & Drug., Lond., 1910, v. 77, p. 828. 

Aspirin. — Cyrus Graham reports a case of acute intoxication 
following the ingestion of two five-grain tablets of aspirin. The 
poisoning resulted in marked oedema of the mucous membranes of 
the eyes, nose and mouth ; to such an extent that the patient could 
hardly breathe. There was also considerable swelling of the head 
and neck, congestion of the conjunctivae and impairment of vision. 
The symptoms disappeared in from ten days to two weeks, but Dr. 
Graham nevertheless believes that aspirin should be listed as one 
of the dangerous drugs and should not be retailed indiscriminately 
to the laity. — /. Am. M. Ass., 1911, v. 56, p. 261. 

Calmine is one of the names under which veronal-sodium, a 
combination of diethyl barbituric acid and sodium, is being exploited 
as a new and absolutely safe hypnotic. The same substance is also 
being marketed as medinal and pharmacists need not be surprised 
to find that thoughtless physicians will combine calmine, medinal 
and veronal in the same prescription. — /. Am. M. Ass., 1911, v. 56, 

p. 137. i-^-^^^i 

Digitalis. — J. Gordon Sharp and J. Lancaster, in a general dis- 
cussion on the time of gathering digitalis and the keeping qualities 
of the tincture, present a number of observations on this important 
drug. They have found that the leaves from wild growing plants 
are frequently contaminated by other leaves. They also point out 
that the leaves themselves, if thoroughly dry are more permanent 
than is the tincture. — Pharm. I., Lond., 191 1, v. 86, pp. 102-104. 

Xravser IT, in a reference to the history of digitalis, points out 
that this drug is receiving a degree of attention which is in strong 
contrast with the neglect it suffered for a century and a half after 



^'"kSirn.''"'} Progress in Pharmacy. 135 

its first introduction into the Pharmacopoeia in 1650, and expresses 
the hope that the time is not far distant when its active constituents 
will be scientifically determined, and their respective value more 
accurately ascertained. — Chem. & Drug., Lond., 1910, v. 77, p. 861. 

J. Burmann has published {Bull. Soc. Chim.) a criticism of 
Keller's method of estimating digitoxin, and says it can only be re- 
garded as valid if it is admitted that the product weighed always con- 
tains true digitoxin in the same proportion relative to the other gluco- 
sides present. He gives the following toxic doses per kilogramme of 
body-weight of rabbits : Merck's crystalline digitoxin, 0.0026 Gm. ; 
digitoxin prepared by Keller's method of estimation 0.008 Gm., or 
9.2 c.c. of a 0.3 per cent, solution in alcohol (7 parts), glycerin (25 
parts), and water (68 parts.) ; Cloetta's soluble digitoxin, 10.3 c.c. 
of a 0.3 per cent, solution in the triple menstruum just mentioned.— 
Chem. & Drug., Lond., 191 1, v. 78, p. 48. 

Ethyl Chloride. — Horatio C. Wood, Jr., reports a statistical 
study on the comparative danger of ethyl chloride as an anaesthetic. 
He finds that the approximate mortality from the use of ethyl 
chloride is 1-6000 anaesthesias while the mortality for nitrous oxide 
is about 1-1,000,000, chloroform 1-3500, and ether 1-15,000 anaes- 
thesias. As the use of ethyl chloride corresponds more nearly to 
that of nitrous oxide, Wood concludes that it must be considered 
as an unsafe anaesthetic.—/. Am. M. Ass., 1910, v. 55, p. 2229. 

FoRMUROL. — The Secretary of the Council on Pharmacy and 
Chemistry of the American Medical Association reports a chemical 
examination of formurol which corroborates the findings of Zernik 
that formurol is not a definite chemical compound but is in reality 
a mixture of hexamethylenamin and sodium citrate. — /. Am. M. 
Ass., 1911, v. 56, p. 210. 

Globularin is the name given to a glucoside obtained from 
Glohularia alypum. It is said to cause an increase, followed by a 
transitory decrease in the amount of urine excreted. — Pharm. 
Zentralh., 191 1, v. 52, p. 52. 

Glycerin. — An editorial in the Journal of - Industrial and En- 
gineering Chemistry (January, 191 1, v. 3, p. 3) points out that the 
manufacture of nitroglycerin explosives is the determining factor in 
regulating the price of glycerin. From being a by-product in the 
manufacture of lead plaster glycerin has become one of the prin- 
cipal products of the saponification of fats and at the present time 
sells at from two to three times the price of the raw material from 
which it is made. 



136 Progress in Pharmacy. { ^"iilS' fm™"" 

Helenic Acid. — Reeb {Nauveaux Remedes^ 1910, 511) has 
extracted from the leaves and flowers of Helenium autumnale a 
crystalline glucoside of the formula (C8Hio02)x. It melts at 161° 
and is of an acid nature, and has therefore been named helenic acid. 
On hydrolysis it yields glucose and a body not further examined. — 
Chem. & Drug., Lond., 191 1, v. 78, p. 48. 

L-suPRARENiN SYNTHETIC is epinephrine produced synthetically 
according to the method of Stolz and Flaecher (Ztschr. f. physiol. 
Chem., V. 58, p. 189). It occurs as a white odorless powder nearly 
insoluble in water, alcohol and ether. It melts at 211 to 212° C, 
and, as its name indicates, has the power of rotating polarized 
light to the left. This substance has the chemical and physical 
properties and produces the physiologic effect of natural epinephrine 
obtained from suprarenal glands. — /. Am. M. Ass., 1911, v. 51, 
p. 120. 

L-suPRARENiN SYNTHETIC BiTARTRATE is the acid tartrate of 
1-suprarenin synthetic. It occurs as a white odorless powder readily 
soluble in water, yielding an acid solution. It melts at 149° C. and 
rotates polarized light to the left. — Ibid. 

Niemeyer's Pill. — James Tyson asserts that the name " Nie~ 
meyer's Pill " is being erroneously applied to the well-known pill 
of calomel, squill and digitalis. This pill antedates Niemeyer, and 
if known by any name it should be that of Addison or Guy. 

The true Niemeyer pill is composed of one grain of quinine, one- 
half grain of digitalis and one-quarter grain of opium, and was used 
by that physician for the fever of pulmonary tuberculosis. — /. Am. 
M. Ass., 1911, V. 56, p. 2X1. See also p. 443. 

Phenolphthalein, Action of. — Fritz C. Koehler reports an 
experiment made upon himself, to determine the factors influencing 
the action of phenolphthalein as an aperient. He found that while 
o.io Gm. of phenolphthalein had a distinctly laxative action under 
ordinary conditions and when the feces reacted alkaline a much 
larger dose had no effect when the diet was regulated to produce 
an acid reaction of the feces. — Schzimz. Wchnschr. f. Chem. ii. 
Pharm., 1910, v. 62, p. 802. 

Poppy. — M. G. J. M. Kerbosch reports a comprehensive study 
to determine where and when the important opium alkaloids are 
formed in the growing plant. He concludes that seeds of Papaver 
somniferum L. contain a trace of narcotine and amorphus alkaloid. 
The germinating seeds have an increased narcotine content and the 



^""kSch,' mi!'"'' } Philadelphia College of Pharmacy. 137 

sequence in which the alkaloids are found in the growing plant is 
narcotine, codeine, morphine, papaverine and thebaine. The first 
four of these alkaloids occurring in plants that are from 5 to 7 cm. 
high. — Arch. d. Pharm., Berl, 1910, v. 248, pp. 536-567. 

The Phosphorus Match. — A recent editorial in the Journal 
of Industrial and Engineering Chemistry (January, 191 1, p. i) con- 
tains some rather interesting information regarding the origin and 
development of matches and the dangers attending the exposure to 
fumes of phosphorus. The earliest known matches, made in 1812, 
were tipped with potassium chlorate and sugar and ignited by sul- 
phuric acid. The phosphorus match was introduced by Derosne in 
1816, and because of the danger attending its manufacture has been 
prohibited in nearly every European country, preference being given 
abroad to the so-called safety matches or to matches tipped with a 
composition containing one or the other of the sulphides of phos- 
phorus. 



PHILADELPHIA COLLEGE OE PHARMACY.* 

By Howard B. French, President. 

Since the world began the inspiration of association has stirred 
the hearts of men, enlightened their minds, strengthened their hands 
and ennobled their lives. The spirit of great acts lives throughout 
the years, creating and forwarding movements which bless man- 
kind. 

When the climax of the long night of colonial injustice and 
oppression had been reached, and the representatives of a suffer- 
ing people came together in 1774, to consider ways and means 
of reHef, they wended their way to a spot already historic, where 
the fires of liberty had been lighted and where the voice of the 
coming nation of freemen had been heard, demanding just recog- 
nition of the inalienable rights of man. As though directed by 
the finger of fate, building better than they knew, a few years 
before, in 1771, a little company of men, drawn from the humbler 
walks of life, in the City of Penn, honest and faithful toilers, 

*An address covering some of the interesting facts in the history of the 
College and delivered at a banquet given by the president at the Union 
League Club, Philadelphia, in commemoration of the ninetieth anniversary 
of the College, February 23, 191 1. 



138 Philadelphia College of Pharmacy. {^mIu'u mV"'' 

helping to lay the foundation and build the superstructure of a 
mighty republic, had reared a meeting place which was now to be- 
come the scene of events memorable while time shall last. 

Very few of the delegates to the Carpenters' Hall Assembly 
knew or had ever heard of this unpretentious building, modestly 
located back from the main street of the city, as though seeking 
an undiscoverable retreat. From the Colonies far and near, they 
came, and under the guidance of the God of nations, whose pro- 
tection they wisely and devoutly sought at the very beginning, they 
solemnly and courageously deliberated. Their just and patriotic 
conclusions met with an instant and hearty response in the hearts 
of the people. They made Carpenters' Hall a Mecca for unborn 
generations, a place where the men of the future might safely seek 
counsel and wisdom. 

As the present representatives of an honored and beneficent in- 
stitution, it is our privilege to remember with pride and satisfaction 
the fact that its founders first met where the patriotic leaders of 
revolutionary days first assembled. It could not have been other- 
wise than that they too should have built wisely and well. 

During the fifty years of its existence, from 1770 to 1820, 
before its temporary occupancy by the founders of the Philadel- 
phia College of Pharmacy, Carpenters' Hall had a peculiarly event- 
ful history. It had its singular vicissitudes, and at one time was 
nearly lost sight of as a place worthy of lasting public honor. Yet 
within that period, it was the scene of events of surpassing im- 
portance. The Provincial Assembly of Pennsylvania met there in 
July, 1774, and in September and October of the same year, the 
first American Congress. In 1775 a conference was held in this 
Hall of far-reaching effect upon the development of trade and 
commerce in America. This was an assemblage of prominent 
financiers and manufacturers interested in the establishment of the 
cotton and woollen industry in this country. The following year, 
in 1776, the Provincial Committee met and resolved to call a con- 
vention to form a government for Pennsylvania, which should re- 
ceive all its authority from the people only. When, liberty having 
been achieved, the problem of the hour was the formation of a 
national government which should stand the storms and trials of 
the years to come, here again, in 1787, came the chosen coun- 
sellors of the people to frame that immortal document — the Con- 



^'^^MSm""' } Philadelphia College of Pharmacy. 139 

stitution of the United States — which the greatest EngHshman of 
the nineteenth century declared the wisest instrument ever con- 
ceived by the mind of man. In 1791, the first Bank of the United 
States commenced business in Carpenters' Hall, continuing therein 
for six years. 

With extraordinary self-forgetfulness, it was at this time, the 
company owning the Hall, now so historic and sacred, withdrew 
from it, so far as their meetings were concerned, and for two 
generations met in an adjoining building. The Bank of the United 
States was succeeded, in 1797, by the Bank of Pennsylvania, for a 
short period. From 1802 until 181 7, the Federal government there 
collected its custom duties. After this came the second Bank of 
the United States. Successive occupants in different parts of the 
building represented the literary, scientific, benevolent, educational 
and musical interests of the city. 

For a time Friends met in the Hall for worship, consecrating 
its wall to spiritual things. In 1833 the Supreme Court of Penn- 
sylvania held its sessions in this building. In 1859 City Councils 
sought to purchase the Hall, on account of its historic interest and 
association, but the proposition was respectfully declined. Having 
been carefully restored and maintained in its primitive simplicity, 
the old Hall has been in sole possession during the past sixty years 
of the Carpenters' Company. Its history should ever inspire men 
to unselfish purposes and lofty deeds. 

The spirit which actuated the founders and early trustees of the 
Philadelphia College of Pharmacy is most impressively illustrated 
on the pages of the minute books of the institution. These earnest 
minded men never lost sight of the great objects to be attained, 
the correction of trade abuses and the elevation of their calling, 
the extension of knowledge and the consequent inestimable service 
to mankind. One of the first matters considered, following organiza- 
tion, was careful revision of the existing pharmacopoeia, in accord- 
ance with the latest accepted standards, every formula to be 
satisfactorily tested before approval. Exceeding care was exercised 
in the election of members of the association and in the selection 
of trustees and members of the faculty of the College. Only men 
of the highest intelligence and recognized probity were entrusted 
with the direction of its affairs. The name was early changed from 
the Philadelphia College of Apothecaries to the Philadelphia College 



140. Philadelphia College of Pharmacy, {^^a^h,' liJiP" 

of Pharmacy. Evincing an earnest desire for the newest informa- 
tion on trade and professional subjects, at a meeting in December, 
1822, a subscription of $25 to the best periodicals relating to 
pharmacy was authorized. At the same meeting, the Board of 
Trustees presented an encouraging report of the work of the Col- 
lege during its first two years. Difficulties had been cleared away, 
much progress made and the outlook was all that could be desired. 
It was added : " To guard against future abuses and to rectify 
those existing in the preparation and sale of medicine, to extend our 
knowledge of pharmacy and to improve the science, may be con- 
sidered the prominent objects of the institution." These, indeed, 
were never lost sight of. The school had been established and now 
a library was a pressing need. There was a further review of the 
care exercised governing the question of conferring degrees, it being 
determined that this privilege should only follow the most faithful 
and efficient study. The duty of continuing to guard the public 
against the imposition and peril of impure and fraudulent drugs 
was emphasized anew. 

In the report for 1823 it was stated that there were upwards 
of one hundred books in the library. In view of our present great 
library, covering all departments of pharmaceutical study, this state- 
ment sounds pathetic. In this report, first mention is made of the 
imperative need of a cabinet of specimens. The founders looked 
abroad for knowledge. At a meeting in September, 1823, a trans- 
lation of the proceedings of the Society of Pharmacy of Paris was 
read to attentive listeners ; also a translation of an article in the 
" Journal de Pharmacie," on the best method of preparing a certain 
syrup. A committee was appointed to continue this enlightening 
work. At a meeting in November of the same year, a loan of 
$1000 was authorized towards the library and a cabinet of speci- 
mens. This was a bold step, confidently taken. This loan was 
carried for a number of years and there was great rejoicing when 
it was paid off. There were no multi-millionaires in those days, 
to hand around vast sums for public entertainment and enlighten- 
ment. 

At a meeting in October, 1824, an important step was taken 
in asserting and maintaining the dignity and honor of the pro- 
fession of pharmacy and of the dealers in medicine. This was the 
adoption of a resolution referring to a growing demoralizing custom 



'^'^S.'m™'} Philadelphia College of Pharmacy. .141 

of secret partnership between physicians and druggists, it was 
vigorously declared: " The Philadelphia College of Pharmacy views 
all such combinations as disreputable and unfair and it recommends 
to its members to abstain from them and to discourage them as far 
as possible." A copy of this resolution was sent to the Philadelphia 
College of Physicians and to the Philadelphia Medical Society, both 
of which organizations heartily endorsed the declarations made. 
The College of Physicians asked co-operation in a movement to 
prevent druggists from compounding medicine for customers with- 
out a physician's prescription, and the College of Pharmacy promptly 
acceded to this timely request. 

In March, 1825, the Journal of American Pharmacy " was con- 
ceived and the first number issued a year later. At the last meeting 
in December, 1828, it was decided to present a gold medal to the 
student presenting the best thesis for graduation, the subject to 
be " a full and original analysis in vegetable chemistry." 

A Committee Report submitted April 27, 1829, said : " The Phila- 
delphia College of Pharmacy has now been in existence for more 
than eight years. During that period it has, with slender funds 
and through many discouragements, effected more for the improve- 
ment of American Pharmacy than all that has before been done or 
attempted in this country. It has produced union and concert, a 
more liberal spirit and more elevated views among the apothecaries 
of Philadelphia. It has had the honor of establishing the first school 
of Pharmacy, which this country has seen. It has established the 
first and only American journal devoted exclusively to the science 
and art of the profession. It has resolved a company of shop- 
keepers into a scientific association. It has educated young men 
with more accurate science and more extensive knowledge than their 
predecessors." At this time also, it was decided to take another 
step forward, through the creation of a loan of $1000 for the pur- 
pose of purchasing the most approved chemical and philosophical 
apparatus for the use of lecturers of the College. The publication 
committee found itself facing serious problems from time to time. 
Reference is pathetically made to the " awful chasm " consequent 
upon delinquent subscribers and those withdrawing subscriptions to 
the " Journal of Pharmacy," yet they courageously go forward, 
confident in the belief of renewed support. It was slow work, 
educating the trade and profession to support periodical publica- 
tions. 



142 Philadelphia College of Pharmacy. { ^"'jii^;!:.": S l*"' 

At the beginning of 1831, there were only about forty-five stu- 
dents assured for all the lecture courses. But the College authorities 
felt encouraged in the belief that its work was destined to widely 
extend, as its character became more favorably known. 

In 1838 the graduating class numbered only nine, and this, seven- 
teen years from the beginning. The curriculum could not be 
compared with that of to-day, yet it was a severe test for those 
days. 

In 1838 Thomas P. James was elected a member of the college. 
Twenty-seven years later this gentleman's drug house, No. 630 
Market Street, was bought out by my father's firm, French, Rich- 
ards & Co., after the destruction of their establishment at Tenth 
and Market Streets by fire. 

The first Minute Book covers the years 1821 to 1841, inclusive. 
The second Minute Book, beginning 1842 and running to 1870, 
contains a most interesting tabulated statement relating to the 
officers of the College, over which we might absorbingly linger. 
It is a record of noble, earnest, unselfish service on the part of 
men worthy of lasting honor. The names of twenty-eight sub- 
scribers to the first building fund, the old hall in Zane Street, are 
given, that of Dr. Geo. B. Wood near the top, for $800.00. Here 
are the names of five presidents, from 182 1 to 1885, who served 
an average of thirteen years each; Daniel B. Smith served twenty- 
five years and Dillwyn Parish sixteen years, he having filled the 
more laborious office of secretary for twelve years previously. Many 
other officers served long terms ; Charles Ellis was secretary four- 
teen years and president fifteen years. Henry Troth served in the 
vice-presidency thirteen years, mostly occupying the chair at stated 
meetings. To the fidelity, energy and wisdom of these officers of 
the first half century of its existence, the Philadelphia College of 
Pharmacy owes an immense debt of gratitude. 

At a special meeting in November, 1847, ^ memorial to Congress 
was adopted, directing attention to the importation of impure and 
adulterated drugs and asking the enactment of efficient legislation 
to prevent a continuance of this growing evil. This suggestion was 
complied with. 

March 31, 1848, the first Code of Ethics was adopted, the Col- 
lege asking its endorsement by the College of Physicians and other 
medical bodies. This was an important advanced step taken and 
the effects have been far-reaching and lasting. 



^\i^^hm.TT^} Philadelphia College of Pharmacy. 143 

The graduates of 1851 numbered 19; those of 1854 reached 26; 
those of 1856 numbered 28, with 112 students enrolled. The 
College was steadily marching onward and upward. The gradu- 
ates of 1869 numbered 48; those of 1870, 51 ; and for many years 
past the roll has numbered considerably over a hundred. 

At a special meeting December 10, 1867, the first steps were 
taken to purchase the present site of the College buildings, and in 
the autumn of the following year, the institution was removed to 
its present location, Tenth Street below Race. At the forty-seventh 
annual meeting, March 30, 1868, the following quaint "farewell 
minute " was read and adopted : 

" The members of the College are reminded that the present 
is the last meeting of the College within the walls of the present 
building, where, for many years they have so pleasantly conferred 
together. On separating, and bidding adieux to the present locahty, 
they hope that their next regular assembling will be under pleasant 
auspices in a building much better adapted to the growing neces- 
sities of the College, and that each member will feel a renewed 
interest in the Philadelphia College of Pharmacy." 

Renewed interest was awakened ; and during the forty odd years 
the College has continued to occupy its present home it has un- 
ceasingly grown, and strengthened, and developed in every direction 
until it stands to-day, as it justly merits, at the head of all in- 
stitutions of the kind in the world. 

In the ninety years of its existence about 20,000 students have 
been instructed ; some of these are widely known as the brightest 
and most successful professional and business men of the time, 
measuring up to a very high standard of learning and efficiency. 
And it is of more than ordinary interest to note, that it is a rare 
exception to find a large pharmaceutical establishment in the United 
States that is not directly or indirectly under the management of 
a graduate or former student of the Philadelphia College of 
Pharmacy. 

With a commanding college home furnished with all scientific 
paraphernalia of the most modern type ; splendidly equipped de- 
partments of research and experiment ; advanced courses of in- 
struction that would have appalled the early graduate ; a corps of 



144 Philadelphia College of Pharmacy. { '"^'"m^^S'; ^jn!""' 

instructors thoroughly competent, enthusiastic and zealous in the 
performance of their special duties, in every way equal to the most 
exacting- demands of the times — our College occupies a foremost 
position in the line of scientific discovery and practical utilization 
of new ideas according to the most approved methods. It is a 
self-confident leader, not a timid follower. 

Having a just pride in the past which has a record rich in 
usefulness and honor, it behooves us to push on to still higher and 
greater things that the achievements of the future may meet our 
highest and worthiest expectations. 



PHILADELPHIA COLLEGE OF PHARMACY. 

NINETIETH ANNIVERSARY. 

Some weeks ago the president of the Philadelphia College of 
Pharmacy sent the following invitation to the officers, members of 
the Board of Trustees and faculty, the Mayor of Philadelphia and 
the heads of our sister institutions : 

Mr. Howard B. French 
requests the pleasure of 



Company at Dinner 
Thursday evening, February 23, 191 1, 
at seven o'clock, 
Union League Club, 
In celebration of the Ninetieth Anniversary 
of the founding of the 
Philadelphia College of Pharmacy 
at 

Carpenters' Hall. 

While the members of the college recognize the significance that 
must necessarily be attached to the attainment of the centenary 
of the founding of the oldest college of pharmacy in this country, 
as shown by the appointment of a committee even at this early date 
to devise and consider plans for the celebration of its one hundredth 
anniversary in 1921, it is probable that the members for the most 
part had not considered the desirability of observing its ninetieth 
anniversary, and hence this invitation from President French must 
have come as more or less of a surprise. 



^'^S. mif'""} Philadelphia College of Pharmacy, 145 

It showed, however, how closely he is in touch with the progress 
of events and how much he has at heart the work of the college. 
The dinner was held in the celebrated banquet hall of the Union 
League, where all of the official dinners in honor of great events 
or the achievements of distinguished men were formerly held. On 
the historic oval table around which the diners gathered was a mag- 
nificent display of flowers, including freesia, narcissus, antirrhinum, 
and lilacs with a background and setting of Smilax laurifolia and 
fronds of the Boston fern. The menu, which was well selected, was 
served in accordance with the service of this famous club. 

The printed menu was in the form of a booklet, which contained 
a list of the names of the officers, faculty and instructors of the 
college and of the invited guests, and was bound in Morocco leather 
with an imprint of the seal of the college and twO' illustrations, the 
one showing Carpenters' Hall where the college was organized in 
1 82 1 and the other, the present college building. On the last page 
inside the cover were the words, " Organized, 1821, P.C.P. Progres- 
sing 191 1." 

At the conclusion of the dinner the host, President French, read 
an interesting historical sketch of the college, which is published 
in another part of this issue of this Journal. He then called 
upon Hon. John E. Reyburn, Mayor of Philadelphia, who delivered 
a most earnest address on the relationship of the institutions of 
learning to the city. He was generously applauded for his remarks, 
in which he said that he hoped that it would be possible to bring 
all of the educational institutions of Philadelphia together at a 
common centre on the new Parkway Boulevard. He further stated 
that his idea was not that they be absorbed or lose any of their 
individual character, but that they might derive all of the benefits 
of close association and neighborly contact. Hon. Henry F. Walton, 
President of the Medico-Chirurgical College, was the next speaker, 
and he heartily endorsed all that the Mayor had said in regard to 
the importance of the close association of independent schools and 
then remarked that he was pleased to bring the felicitation of the 
Medico-Chirurgical College to the officers and faculty of the Phila- 
delphia College of Pharmacy gathered on this eventful occasion. 

Dr. J. W. Holland, dean of Jefferson Medical College, said that 
he brought the warmest congratulations of the " twin-sister " of the 
Philadelphia College of Pharmacy. Tie stated that while Jefiferson 
was founded four years later than the Philadelphia College of 



146 Philadelphia College of Pharmacy. {^'"'^^S f.!',*""- 

Pharmacy, her first grackiating class was sent forth in 1826, which 
was the time of the graduation of the first class of the Philadelphia 
College of Pharmacy. He also referred to the fact that while a 
number of students of the Philadelphia College of Pharmacy had 
gone to Jefferson Medical College, this college also gave to the 
medical faculty of Jefiferson, Professor Franklin Bache, who was 
connected with the faculty of Jeft'erson Medical College for seven- 
teen years. Brief addresses were also made by Vice-President Jos. 
L. Lemberger, and Professors Remington, Sadtler, Kraemer and 
Moerk. 

The addresses of the Mayor and some of the other speakers not 
only hinted at the general scheme for the improvement of Philadel- 
phia, which has been worked out by experts in their respective lines, 
but showed that the scheme comprehends a more or less definite 
plan for the improvement and, to some extent, co-ordination, of the 
educational institutions of the city. In addition, a fresh impetus 
was given the active workers of the college by the opportunity 
afforded to commingle at the same board and by reason of the 
rehearsal of the ideals and deeds of those who had gone before, to 
press forward to the century mark with renewed zeal and earnest- 
ness. The occasion was one which w^as encouraging to the older 
men who had been actively engaged in the work for these many 
years, and likewise an inspiration to the younger men upon whom 
the responsibilities of the future rest. 

H. K. 



NOTES AND NEWS. 

A PORTRAIT OF PRESIDENT FRENCH will be presented to the Col- 
lege at a testimonial dinner to be given at the Union League, on 
Tuesday, April 4, 191 1, at seven o'clock. This promises to be one 
of the most interesting occasions in connection with recent affairs 
of the college. 

A Handy Reference Book. The Druggists' Circular has re- 
cently published the second revised and enlarged edition of their book 
on " The Modern Materia Medica." This work contains much 
valuable information regarding the description, tests, therapeutic 
action and doses of all of the newer substances that are likely to 
be prescribed, and will be found of very great assistance to the prac- 
tical druggist who is expected to know something of these things 
at a moment's notice. 



THE AMEEIOAN 

JOURNAL OF PHARMACY 

APRIL, ipii 



A REVIEW OF THE CHEMICAL WORK DONE ON THE 
ACTIVE PRINCIPLE OF ERGOT. 

By Alfred C. Crawford, 
Pharmacological Laboratory, Leland Stanford, Junior, University. 

Biological tests have shown that different ergots vary much 
in their activity ; some are apparently devoid of any medicinal or 
poisonous action. This inactivity has not yet been proved to be 
associated with definite macroscopic peculiarities of ergot, or with 
peculiarities of the host upon which it grows. Ergot grown on 
rye is what is officinally referred to under the term ergot. 

The biological method of testing ergot has been much discussed 
in recent years. For a long time the majority of investigators rested 
content in the belief that the principle which produced the bluing 
of the cock's comb was the one to which the therapeutic action of 
ergot was due, and that on this basis the drug could, at least 
approximately, be standardized for clinical usage. Later investiga- 
tions tended to discredit this view, suggesting that the principle 
or principles which induce uterine contractions may not necessarily 
be those which cause bluing of the cock's comb, and that the latter 
may have a subordinate role in medicine. 

Owing to the peculiar chemical difficulties inherent to this 
subject, our knowledge of the active principles of ergot has been 
based largely on so-called pharmacological isolations, which have 
not answered strict chemical requirements. To form any accurate 
idea as to the methods for the standardization of ergot it is 
necessary to know something of the historical development of the 

(147) 



:48 



Active Principle of Ergot. 



I Am. Jour. Pharm. 
1 April, 1911. 



work done on the isolation uf the active principles. Unfortunately 
various investigators have used the same name for different prepa- 
rations, and have used different biological tests as their guide 
in determining the activity of such preparations, so that, for clear- 
ness it is necessary to discuss in some detail the work of each, 
although the names of these workers are now unimportant. 

Ergot has been used by the Chinese as an oxytocic for over 
one thousand years, but there are only a few records of its use 
in modern medicine until Steam's article^ (1807) appeared. The 
earher workers were engaged in proving the relation of ergot to 
the various complex-of-symptoms wdiich have received the name 
"ergotism."" Salerne ^ (i754) Tessier (1778) found that 

gangrene occurred in young pigs after the administration of ergot, 
while Dietz (1830) noted that one to three ounces of ergot would 
cause gangrene of the comb and wings of birds. From an early 
date ergot was believed to possess a specific action upon the uterus 
and the small arteries. 

The recorded chemical work on ergot dates back to 171 7, but 
the reports of the early investigators, such as Tessier,* Mass, Pet- 
tenkofer (1817), and others need only be referred to. In 1817 
Vauquelin and in 1831 Wiggers called attention to the large 
amount of oil in ergot. Wiggers denied the presence of hydro- 
cyanic acid in it. This acid had been obtained by Pettenkofer 
by burning ergot with caustic potash, but Roberts believed he 
had obtained a reaction for it in an aqueous extract. Wiggers 
recognized a sugar which Liebig and Pelouze claimed to be mannit, 
while others believed it to be mucose.^ This mucose has been 
found to be trehalose.' Later both mucose and mannit were 
claimed to be present in ergot. 

Wiggers removed oils, etc., from ergot by means of ether 
and extracted the residue with alcohol. The portion of this ex- 
tract which was insoluble in water he called ergotin. This must 
necessarily represent a mixture and not a chemical individual. He 
fed 9 grains of this ergotin to a cock and induced convulsions and 
death. This amount corresponded to about one and one-half ounces 
of ergot. He noted that the comb became cold, but said nothing 
as to its bluing, and inferred that ergotin represented the toxic 
principle, while the aqueous extract represented the therapeutically 
active agent, the active principle was believed to reside in the 
aqueous extract and was probably due to a so-called " ozmazom." 



Am. Jour. Pharm. | 
April, 1911. / 



Active Principle of Ergot. 



149 



Dietz found that the aqueous extract of ergot possessed the same 
action as ergot itself, while Schrofif ^ claimed, that in man, Wig- 
gers' ergotin produced the essential symptoms seen after ergot 
administration. Wiggers also obtained a wax-like body which he 
called cerin. 

In 1840 Wright,-^ from clinical observations and also from ex- 
periments on dogs and birds, claimed that the oil obtained from 
ergot contained the active principle. This oil was extracted from 
ergot by means of ether. Sir J. Y. Simpson in speaking of this 
oil said, " I have repeatedly employed your preparation of the 
ergot, and have always preferred it of late, because it has ap- 
peared to me to act with more precision than the infusion of the 
powder, and its dose is more easily regulated. I have used it both 
in cases of lingering parturition, dependent on deficient uterine 
contractions, and also in instances of post-partum hemorrhage." 
Wright imagined that the oily body obtained by distilling dry 
ergot, and that obtained by treating ergot with liquor potassse, was 
the same as the one which may be obtained by extraction with ether. 
Perhaps the differences may explain certain variations in the reports 
as to the action of this oil. No doubt in these extractions of oil 
various compounds were contained. 

The name ergotin was also used by Bonjean (1842) for an 
aqueous extract freed from some extraneous matter by precipita- 
tion with alcohol. It was not claimed to be a definite chemical, 
but rather a pharmaceutical preparation. The ergotin of Bon- 
jean was also called Extractum hsemostaticum," as he believed 
it to be an efficient agent for controlling hemorrhage. Bon jean 
denied that Wiggers' ergotin was active. He noted that after the 
administration of ergot, animals developed a " narcotic " condition, 
which he compared to that resulting from the administration of 
morphine, and called attention to the fact that the combs and 
wattles of cocks turned blue. Bon jean said the principal thera- 
peutic agent was the aqueous extract, but that the poison was an 
oil, soluble in ether. This oil lost its poisonous property bv being 
boiled. Kohler,^^ by experiments on frogs, showed a difference in 
activity between the ergotin of Wiggers and Bon jean's preparation. 
Schroff noted that i gm. of Bon jean's ergotin caused abortion 
in a rabbit. 

Hooker 1- (1852) found that the oil extracted by ether slowed 
markedly the pulse rate in a young man. This slowing of the 



I50 Active Principle of Ergot. {^'^\iZ':mi.'''^' 

heart by ergot and its preparations was also called attention to 
by a number of workers. Hooker inferred that the capillary circu- 
lation was disturbed, because " a portion of the skin deprived of its 
blood, by pressure with the finger, being a long time in recovering 
its color " and noted that there was also an increased secretion of 
urine. According to him, the ethereal extract possessed no ecbolic 
action, but the residue after the extraction still exerted this action. 

Parola claimed that the oil obtained from ergot was inactive 
and that the activity of ergot was to be traced to a resin extracted 
with the oil. However, the term resin is apt to be a vague one. 
Betrand,^* by experiments on himself and on animals, corroborated 
Parola's statements as to the inactivity of the oil. ArnaP^ (1848) 
claimed that neither the ethereal nor the aqueous extract contained 
the real toxic principle, but that it resided in the residue after such 
extractions. He believed the hemostatic action of ergot to reside 
in the aqueous extract and to be associated with the depressant 
action on the heart, and claimed that the irritation of the in- 
testines was an important feature of the action of ergot. He also 
noted that the aqueous extract acted as a diuretic. During one 
day eight grams of ergot were given tO' a cock; and on about the 
seventh day, the bird became dull. In some cocks similarly fed, 
the comb turned blue ; in others, there were ulcerations of the comb 
with emaciation and death. 

Herrmann made the interesting observation that the evaporated 
ether — extract of ergot, on treatment with alkalies, developed the 
odor of ammonia and of trimethylamin. 

Winckler in 1827 recognized a volatile base which he called 
secalin (propylamin) , and believed that the ergotin of Wiggers 
was a combination of resin with propylamin. This propylamin 
was later found to be trimethylamin, although at one time it 
was believed to be methylamin.^^ Gerres,^^ in 1862, unfamiliar 
with Winckler's work, also reported the presence of a volatile base 
which he named secalin and noted that an aqueous extract when 
shaken with sodium bicarbonate and ether imparted the odor of 
ergot to the ether. He also observed that on evaporating a tartaric- 
acid-alcohol extract of ergot and shaking the evaporated mass with 
sodium bicarbonate and ether it yielded a residue which produced in 
a rabbit acceleration in the pulse-rate and trembling. 

In 1864 Wenzell described a volatile acid, which he named 
ergotic acid, and also two amorphous bases which he described as 



Am. Jour. Pharm. ) 
April, 1911. / 



Active Principle of Ergot. 



alkaloids. He precipitated an aqueous extract of ergot with lead 
subacetate to remove impurities and then precipitated the filtrate by 
means of mercuric chloride and bicarbonate of potassium. After 
decomposing this precipitate with H^S, the two bases were separated 
by means of mercuric chloride. As its name would imply, he 
believed the first base to be the medicinally active agent, however, 
no analyses were made of these compounds. This view that 
ecbolin was the active agent in ergot was based on its supposed 
action on the spinal cord of man, which action manifested itself 
by involuntarily muscular contractions, etc. The activity of ecbolin 
was also inferred from one experiment in controlling uterine hemor- 
rhage. Wenzell later separated his bases by means of the insolubility 
of ecbolin in ether. On warming- an extract with caustic potash 
an odor of propylamine, in reality trimethylamine, was obtained. 
This work was corroborated by Herrmann as to the presence 
of ecbolin, the only one of Wenzell's bodies he searched for, and 
by Ganser as to the presence of ecbolin, ergotin and ergotic acid, 
while Manassewitz found ergotin only present and with it a form- 
ate. As in Wenzell's experiments, the precipitates which Manas- 
sewitz obtained with mercuric chloride yielded trimethylamine on 
treatment with caustic potash. Haudelin,^* by experiments on cats, 
failed to corroborate Wenzell's work. He found that both the 
precipitate and filtrate with mercuric chloride and sodium carbonate 
were inactive to cats on intravenous injection. He noted that the 
active principle was insoluble in alcohol and could not be precipitated 
with lead subacetate and ammonia. Dragendorff and Podwissotsky 
found both ecbolin and ergotin inactive to' frogs. Rossbach 
claimed that there were only quantitative differences between Wig- 
gers' ergotin and Wenzell's ecbolin. Wenzell noted that the re- 
action of an aqueous extract of ergot was acid, and believed this 
due to the presence of acid phosphate of magnesia. 

Blumberg^^ thought there was only one alkaloid present in 
ergot and that ergotin and ecbolin were identical. The filtrate from 
which Wenzell obtained his ergotin was found by Blumberg to 
yield trimethylamin, while the precipitate which should contain 
ecbolin yielded none. 

According to Kobert, the compound which excites uterine 
action has nothing to do with the substance which forms the 
main mass of Bon jean's extract and of Wenzell's dialyzed ergotin. 

Wernich ^® traced the action of ergot to the water-soluble 



Active Principle of Ergot. 



Am. Jour. Pbarm. 
April, 1911. 



sclerotic acid. He used the contraction of the blood vessels of 
the frog as his guide and found that the ether extract of ergot caused 
no contraction of these vessels. His preparation was placed on the 
market as " dialyzed ergotin," the dialysis being used to free it 
from certain extraneous matter. Wernich reported that, after 
ergotin administration, the bladders in numerous cases were found 
distended, owing to an increased secretion of urine. This ob- 
servation agrees with that of Hooker already mentioned. Kokorin 
is reported to have noted that, after injecting Wernich's preparation, 
dry gangrene occurred at the site of injection. 

Buchheim (1874) failed to obtain any active principle, and 
traced the acidity of ergot to lactic acid and its activity tO' decom- 
position products of proteins. His most important work was to 
prove the presence of leucin, which he showed yielded amylamin 
on heating in a test tube. 

Dragendorff and Podwissotsky called attention to the presence 
in ergot of 0.4-1. 15 per cent, phosphoric acid, and strange to say, 
the activity of ergot was traced by Leri to this acid. Its presence 
was originally noted by Vauquelin. Dragendorff and Podwis- 
sotsky somewhat purified sclerotic acid and named it sclerotinic 
acid and traced most of the activity of ergot to it, but some of 
the activity was attributed to a colloid body which they named 
scleromucin. They also noted the presence of a base, picrosclerotin, 
yet they did not attribute the action of ergot to it. Their tests 
were made on frogs and seem unsatisfactory. From experiments 
on pregnant and non-pregnant animals and also on the isolated 
uterus, Kobert claimed that sclerotinic acid did not excite uterine 
contractions, and Ganguillet and Rennert pronounced it worth- 
less for clinical purposes. The clinical experiments of Fehling and 
v. Scanzoni also indicated that sclerotinic acid possessed nO' marked 
therapeutic activity to excite uterine contraction, Dragendorff and 
Podwissotsky also claimed to have proved the presence of various 
coloring matters, sclererythrin, sclerojodin and scleroxanthin 
together with a crystalline body sclerokrystallin. Podwissotsky 
noted that on treating sclerotinic acid with alkalies it lost its 
activity and ammonia developed. The view that the activity of 
ergot was mainly due to sclerotinic acid was corroborated by 
Nikitin's work.^^ 

Zweifel also traced the activity of ergot to a water-soluble 
acid principle, and based his conclusions on the action of this 



A.m. Jour. Pharm. ) 
April, 1911. / 



Active Principle of Ergot. 



153 



preparation on the blood vessels of the frog. He found that 
sclerotinic acid excited uterine contractions in pregnant animals 
without injury to the foetus and that it also induced peristaltic move- 
ments of the intestines and caused contraction of the blood vessels. 
This action on the intestines had been previously noted by Bonjean. 

As it was still a question as to which of these principles were 
responsible for the action of ergot, Denzel,^^ believing the uterine 
action of ergot to be due to all the above constituents, made his 
preparation so as to contain both the bases and the water-soluble 
principle. Mauk found this preparation to be efficient in many 
cases of labor, but Scanzoni and Bumm, on account of severe symp- 
toms which followed its use, reported it unsuited for clinical usage. 

The most important of the earlier chemical work was done by 
Tanret,^^ who reported the presence in ergot of an alkaloid, which 
he named ergotinine. This was probably identical with the picro- 
sclerotine of Dragendorfif and Podwissotsky. Tanret believed that 
ergotinine existed both in a crystalline and in an amorphous con- 
dition, with a preponderance of the amorphous variety. In old 
ergot the crystalline form especially diminished, thus one kilogram of 
fresh ergot yielded 1.2 gm. alkaloid, of which one-third was in 
the crystalline form, but after two years' preservation, a specimen 
of ergot gave 0.4 gm. only of alkaloid, one-fifth of which was crystal- 
line ergotinine. He considered the amorphous alkaloid merely a 
molecular modification of the crystalline form. This latter increased 
the solubility in alcohol of the crystalline variety. He obtained 
ergotinine by extracting crude ergot with boiling alcohol and then 
making the alcohol alkaline, and after evaporation, shaking the 
residue with ether. On the addition of a citric-acid solution the 
alkaloid separated from the ethereal solution and was afterward 
purified. It gave an odor of methylamine when treated with strong 
caustic hydrate. On treating ergotinine with concentrated 
H2SO4, in the presence of a little alcohol, this alkaloid gave a 
yellowish-red color which passed into a blue. Ergotinine solutions 
showed a peculiar fluorescence which was compared with that of 
quinine. Ergotinine was sold under the name ergotininum citricum 
solutum. Besides ergotinine, Tanret also claimed the presence of 
a cholesterine-like body, ergosterin, a base containing sulphur ergo- 
thioneine, and a volatile alkaloid. A volatile coniine-like base 
had been previously noted by Winckler. The ergosterine of Tanret 
is probably the same as Wiggers' waxy-like cerin and the 
cholesterin of Ludwig.^^ 



154 



Active Principle of Ergot. 



( Am. Jour. Pharm. 
\ April, 1911. 



In 1886 Kobert ^' reported a crystalline specimen of ergotinine 
to be inactive on the uterus and that it also failed to produce 
bluing of the cock's comb, although he had in 1883 stated that 
ergotinine (Tanret) would cause marked toxic action in frogs 
and a rise in blood pressure in rabbits. Meulenhoif reported 
ergotinine inactive, however, Blumberg found that 20 mg. would 
kill frogs, while in Palm's hands 0.0 1 gm. caused little or no bluing 
of the cock's comb. The clinical reports of its use also varied. 

Galippe and Budin noted no symptoms in a dog after the 
subcutaneous injection of 30 mg. of Tanret's ergotinine, but 80 
mg. induced colic and vomiting with a lowering of the temperature, 
while a syrup containing 105 mg. of ergotinine induced death. 
One milligram of this ergotinine represented i gm. of ergot. 
IJujardin-Beaumetz noted similar nausea and vomiting to occur in 
man after the injection of 4-5 mg. of this alkaloid. In one case 
puerperal hemorrhage was apparently arrested by it, yet the arrest 
only occurred after hours of delay and there must necessarily be 
an element of uncertainty in this case. Others reported favorable 
clinical action from its use.**^ The confusion in the reports is 
probably due to the fact that some of the specimens used were wholly 
crystalline, while others were a mixture of the crystalline and amor- 
phous varieties. 

In 1884 Kobert announced the presence of three bodies in ergot 
— a base, cornutin, and two with acid properties, ergotinic acid and 
sphacelenic acid. Kobert isolated no body chemically pure. His 
isolations were merely physiological. The term ergotinic acid had 
already been used by Merck for Zweifel's preparation. 

Ergotinic acid subcutaneously injected, acted as a paralyzant 
on the brain and spinal cord, but caused no bluing of the cock's 
comb, and was inactive on the pregnant uterus of sheep, cats, 
rabbits, and dogs. By mouth it was inactive, either being unab- 
sorbed or destroyed in the gastro-intestinal tract. Sphacelenic 
acid received its name from the old name of ergot, Sphacelia 
segetum. Kobert believed the specific action of ergot was due 
to this resinous acid,*^ although he admitted that he had not isolated 
it in a chemically pure condition. Sphacelinic acid caused bluing of 
the cock's comb and had the characteristic action on the uterus. 
Kobert introduced the cock's-comb test as a guide for the recog- 
nition of this acid. Cornutin, except in toxic doses,*^ produced no 
uterine contractions and caused no bluing of the cock's comb, but 



Am. Jour. Pbarm. ) 
April, 1911. / 



Active Principle of Ergot. 



155 



in frogs even 1/32 mg. induced convulsions. However, Meulen- 
hoif failed to note these convulsions. Kobert said distinctly 
that his cornutin was different from the crystalline or amorphous 
ergotinine of Tanret and that there was no resemblance physiol- 
ogically. The ecbolin of Wenzell was probably the same as 
Robert's cornutin. 

Later, Robert modified his original view and stated that 
cornutin would produce uterine movements in pregnant and non- 
pregnant uteri, but in non-pregnant animals the dose must be large. 
Sphacelenic acid produced uterine contractions, tetanic in character 
and associated with toxic symptoms, while cornutin induced nor- 
mal intermittent ones. According to Robert cornutin acted on 
the spinal centre, while sphacelenic acid acted directly on the 
uterus. Cornutin produced marked narrowing of the arteries of 
uterus. The therapeutic action of ergot was believed by Robert 
to be a resultant of the action of both compounds. Palm showed that 
even 0.005 gm. of cornutin would produce bluing of the cock's 
comb with dyspnoea. This preparation freed from ergotinic 
acid was then introduced on the market and used clinically,*^ as a 
hemostatic or oxytocic, generally with success. The work of 
Robert was confirmed by Griinfeld so far as sphacelenic acid was 
concerned and by Lentaker as to cornutin.*^ In Ludwig and Savor's 
experiments the cornutin preparation of Robert failed to produce 
the full characteristic action in cocks, when given in doses corre- 
vSponding to the proper amount of ergot, and with them clinically the 
results were disappointing.^^ Cornutin (Robert) has been tested 
physiologically by Lewitski. He found that 1.5 to 2 mg. per kilo 
of this preparation caused abortion in animals in the later stages 
of pregnancy. He also reported favorable clinical use without toxic 
symptoms. Robert's views were mainly upheld by his pupils. 
According to him, no ergot retained its therapeutic powers over 
twelve months. 

Robert's change of view would suggest that he was dealing with 
a chemically impure body. Tanret considered Robert's cornutin 
a partially altered ergotinine. Robert finally summed up his work 
by saying that there was an inactive and an active modification 
of the ergot alkaloid ; the active one he believed was cornutin 
and the inactive one was the crystalline ergotinin of Tanret. 

Reller's work was based on the idea that an alkaloid is the 
active principle of ergot and on this basis he devised a method 



156 



Active Principle of Ergot. 



( Am. Jour. Pharm. 

t April, 1911. 



of separating the alkaloid or alkaloidal mixture. It is based on 
the experiments of Kobert, which showed that the alkaloid was 
soluble in ether, and on Wenzel's observation that it was insoluble in 
petroleum ether. This more or less pure body Keller has named 
cornutin, on the basis that his preparation is the same as Robert's 
cornutin. The adoption of this name has given rise to much con- 
fusion. Wyss tested Keller's cornutin and claimed that it agreed 
in action with that of Kobert, but the nature of the test is not 
stated; presumably, it was the bluing of the cock's comb. Keller 
at first believed his cornutin was identical with the ergotinine of 
Tanret and the cornutin of Kobert, while the picrosclerotin of 
Dragendorfif and Podwissotsky was considered to be the same 
compound admixed with certain decomposition products. He called 
attention to the fact that cornutin could be precipitated from an 
ethereal solution by petroleum ether. In addition to the color noted 
by Tanret, a sulphuric acid solution of the alkaloid, on the addition 
of FeCls or other oxydizing agents as bromine water, gave an 
orange red which passed into a blue and then bluish green. To 
secure the best results the alkaloid is first dissolved in acetic acid 
and sulphuric acid is then added. 

Later Keller adopted the view of Tanret, that Kobert's cornutin 
was a decomposition product of ergotinine, and showed that his 
cornutin, if treated with acid, yielded a body having the character 
of Kobert's cornutin.^^ He has proposed a method which 
has been used by various firms for quantitative determination 
of the active principle. Keller's method is as follows: Twenty- 
five grams of dried ergot are extracted with petroleum ether 
until the extract gives no residue. After drying with moderate 
heat it is transferred to a weighed vessel of about 250 c.c. capacity, 
and 100 grams of ether are poured over it ; after about ten minutes, 
milk of magnesia, made by shaking one gram of calcined magnesia 
with 20 c.c. of water, is added and the mixture is shaken thoroughly. 
After half an hour 80 grams of the ethereal solution are poured 
ofif. Four grams of the ether solution correspond to one gram 
of ergot. If the solution is not clear, it is allowed to stand, and 
then shaken three times with dilute HQ (0.5 per cent.), using 25, 
15 and 10 c.c. If necessary it is shaken a fourth time with 10 c.c. 
of the same and the last shaking is tested with Mayer's solution 
to see if the extraction is complete. The acid solution is then 
shaken with ether and ammonia, and the shaking repeated twice, 



Am, Jour. Pharm. | 
April, 1911. / 



Active Principle of Ergot. 



157 



then filtered and distilled in a weighed vessel. After treating with 
ether and exaporating, the residue is weighed. The cornutin con- 
tent of six samples of ergot varied from 0.095 to 0.225 P^^ cent. 
According to Dohme, German ergot as occurring on the American 
market assays at 0.15 per cent., Spanish ergot at 0.29 per cent., and 
Russian ergot at 0.18 per cent. 

On frogs (R. Esculenta), Santesson "'^ tested this cornutin in 
doses of 1-20 mg., and as no convulsions were produced, inferred 
that it was therefore different from the cornutin of Kobert, but 
Palm has shown that 0.005 g'^'^^- of cornutin obtained from certain 
ergots by Kobert's method failed to produce convulsions in frogs. 
Meulenhoff reported a similar experience. Evidently the con- 
vulsive action of Robert's body must be due to some accidentally 
present body which may not necessarily be present in all ergot 
preparations. Santesson claimed that in pregnant rabbits Keller's 
cornutin failed to produce any uterine action save in toxic doses. 
Santesson's failure to produce a rise in blood pressure in rodents 
with cornutin does not argue against the presence of a blood- 
pressure-raising principle, as rodents are especially insensitive to 
this action. Santesson, by injecting 5 mg. intravenously into cocks, 
produced a rise in blood pressure, while 15-25 mg. injected 
hypodermically into these animals produced a marked discoloration 
of the comb. 

One of the objections urged by Santesson against Keller's 
work, is that Keller's analysis of an ergot preserved for two years, 
showed a relatively large percentage of cornutin. Ergots long 
preserved are considered inactive, but the clinical work of Bischof- 
berger indicated that two and three year old ergot still caused uterine 
contractions however, one must be careful in interpreting clinical 
experiments. Unfortunately Keller failed to control his analysis 
with physiological tests. Tanret a few years previous had pointed 
out that although the alkaloidal content of old ergot diminished, it 
was mainly the crystalline alkaloid which was lessened. The truth 
of the matter probably is that by Keller's method more than one 
alkaloid is extracted — a view which Keller later adopted. Keller 
made no analysis of his cornutin — of itself a suggestion that he was 
not sure of its chemical purity. 

Several years ago the writer examined the ]3roducts obtained 
during the various stages of the Keller-assay method and found in 
the alkaline-ether-'' shaking " apparently all the principles which 



158 



Active Principle of Ergot. 



f Am. Jour. Pharm. 
I April, 1911. 



caused bluing of the cock's comb, while the residue was inactive in 
this respect. At times it seemed as if the ether-shaking was more 
active than the original fluid extract which was used. This extract 
would induce a marked rise in blood pressure in dogs with cut vagi. 
It must be remembered that besides the alkaloids other bodies, such 
as basic amines, which might contribute to its pressor activity, go 
into this ether. As there is probably more than one body in this 
shaking it seems at present unsafe to trust this method alone. How- 
ever, Keller's method is a safe one for determining the amount of 
bases present, or at least the ether-soluble bases. 

Schaerges states that Keller's cornutin is not present in ergot 
as such, but as ergotinine. Barger and Dale believe this cornutin to 
be a mixture of ergotinine with 25 per cent, ergotoxine. Keller's 
preparation is on the Swiss market under the name " Secornin." 

The next important step was undertaken by Jacob j.^^ He first 
removed from ergot, by means of petroleum ether as much of the 
oil as possible, and then extracted the active principle with 
ether. After this extraction the ergot caused no bluing of the cock's 
comb. The ether was precipitated by means of petroleum ether and 
the precipitate was redissolved in ether and afterwards fractionally 
precipitated by petroleum ether. When dissolved in sodium hydrate, 
0.1 gm. of this precipitate, which contained no nitrogen, caused 
bluing of the cock's comb and did not produce convulsions, while 
a similar injection of from 0.1-0.2 gm. induced regular normal 
uterine contractions with abortion in pregnant animals, unassociated 
with any toxic effects, either to the mother or to the young. In 
some animals, such as cats, its intravenous injection was followed 
by a rise in blood pressure, but usually this action was not marked. 
In these cases the vagi were uncut and the central nervous system 
was intact. However, if the spinal cord was cut, Jacobj noted a 
rise after such an injection. The preparation was named chrysotoxin 
fC^^HooOr,). This yellowish brown body is soluble in ether, chloro- 
form, benzol, alcohol and caustic alkalies, but insoluble in water and 
in dilute acids. Under the influence of an excess of alkali it is 
trcnsformed into ergochrysinic acid which is inactive. However, 
an active combination of chrysotoxin with sodium can be obtained 
b;/ precipitating its ethereal solution with an absolute alcoholic 
solution of sodium hydrate, but in this case an excess of alkali 
is to be avoided. This combination is known as spasmotin. Accord- 
ing to Dale, chrysotoxin contains about 90 per cent, impurities. 



Am. Jour.jPharm. ) 
April, 1911. J 



Active Principle of Ergot. 



159 



If the original ethereal solution is not carefully fractioned with 
petroleum ether the chrysotoxin is admixed with a nitrogenous 
body. When such a precipitate is treated with glacial acetic acid 
a portion only dissolves. The portion which remains undissolved, 
when taken up in ether, gives a precipitate with petroleum ether. 
This has a golden yellow color and is inactive on the cock's comb. 
It has received the name ergochrysin. 

On treatment with sodium carbonate, the acid solution of the 
crude precipitate yielded a gray alkaloidal precipitate which was 
named secalintoxin (C13H24N2O2) • This is about four times as 
active as chrysotoxin in producing bluing of the cock's comb and 
is free from any convulsant action. Secalintoxin has the same 
action as chrysotoxin, but differs from it in degree. Jacobj says 
that under certain conditions a marked rise in blood pressure may 
follow its injection. Secalintoxin is a white powder which is soluble 
in alcohol, benzol, chloroform, and slightly so in ether. It gives a 
violet color on evaporation with an alcoholic solution of HQ. An 
oxalate, a phosphate and other salts were obtained by precipitating 
its ethereal solution with the corresponding acids. It was noted 
that on standing, the oxalate separated into two portions, one less 
soluble than the other, but this did not suggest to Jacobj that they 
were possibly two oxalates. 

When the precipitate of secalintoxin is dissolved in a mixture 
of ether and alcohol and treated with petroleum ether, a greenish 
mass is precipitated along with some crystalline needles. Jacobj 
believed that by this means he had separated the basic portion 
of secalintoxin, but one would hardly expect such a method to 
free a base from its comhination. These needles have received the 
name secalin and their formula was determined to be C29H55N6O14. 
They gave a violet colored reaction with alcoholic HCl. These 
crystals are presumably the same as Tanret's crystalline base. 
Jacobj expressed a doubt as to this identity, on the ground that his 
N. determinations did not agree with those of Tanret, but it has 
since been shown that Tanret's figures are too high and should 
be close to those of Jacobj. Even 40 mg. of these crystals failed 
to produce bluing of the cock's comb, and they were also devoid 
of convulsant action. The greenish precipitate with which these 
crystals were mixed, in 0.005-0.008 gm. doses caused bluing of the 
cock's comb. Jacobj believed this resinous, readily-decomposable 
body to be the active principle of ergot, and has named it sphacelo- 



i6o 



Active Principle of Ergot. 



/Am. Jour. Pharm. 
I April, 1911. 



toxin, because Schmiedeberg had previously used the term for the 
unknown active constituent of ergot. The combination of ergo- 
chrysin with sphacelotoxin was named chrysotoxin and that of secaHn 
with sphacelotoxin was designated secalintoxin. Palm corroborated 
the activity of Jacobj's preparation by clinical observations and also 
by animal experiments. 

Meulenhoff essentially corroborated Jacobj and stated that 
the active principle of ergot was sphacelinic acid. This he be- 
lieved identical with sphacelotoxin but retained Robert's nomen- 
clature, using the term sphacelinic acid. He claimed the presence 
of but one alkaloid, ergotinine, which he considered only partly 
active. Robert claimed that spasmotin was weaker than his sphace- 
linic acid and warned against its clinical use, as he believed that 
it was merely sphacelinic acid and had all its disadvantages. 

Rielander has corroborated the work of other investigators 
in finding both betain and cholin in ergot. By injection he showed 
that these bodies were not responsible for the local gangrene which 
appears at the site of an ergot injection. In addition to these 
compounds he found both tetra- and penta-methylendiamin. As 
to whether these exist as such in ergot or are products from the 
reagents is not proven. Ludwig,^^ years before this, claimed that 
methylamin was present in ergot, while Ganser denied that methyl- 
amin, or trimethylamin existed as such in ergot. Tanret traced 
methylamin to the decomposition of his ergotinine. It is to be 
presumed that the free ammonia which Vauquelin suspected to 
be present may be in reality an amine. 

Vahlen has recently introduced a crystalline principle, which 
he obtained by evaporating the aqueous extract of ergot and ex- 
tracting the residue with hot alcohol (75 per cent.). On cooling 
this alcohol crystalline needles, which he named clavin, separated. 
The crystals varied in form when other methods of separation were 
used. They melt at 262-263° C. and are soluble in water, and 
their solution reacts neutral to litmus. Clavin is not precipitable 
by caustic alkalies, by alkaline carbonates or by alkaloidal reagents, 
and is insoluble in petroleum ether, ether and absolute alcohol. 
Vahlen was unable to determine accurately the yield of clavin, but 
stated that one kilogram of ergot yields a few grams of this substance. 
He has calculated the empirical formula to be C11H20N4O2, and 
believes, on the basis of his molecular weight determination, that in 
aqueous solution it dissociates into two bodies which have approxi- 



Am. Jour. Pharm. ) 
April, 1911. / 



Active Principle of Ergot. 



i6i 



mately the same molecular weight. Barger and Dale object to this 
determination in glacial acetic acid and believe Vahlen's formula 
incorrect. 

Vahlen noted that on heating these crystals the reaction resembled 
that with leucin, an amino-acid which Buchheim had previously 
found in ergot. According to Vahlen, when 0.194 gram of clavin 
was injected into the vein of a cock, it produced no bluing of 
the comb; it is probably devoid of toxicity, as 2.6 grams per kilo 
injected subcutaneously into mice produce no symptoms save some 
dulness. According to him, the second constituent could be repre- 
sented by the formula C5H11O2N, although its structure is as yet 
unknown, and he believes that it is the physiologically active con- 
stituent of clavin. This is claimed on the basis that, as clavin is 
active and leucin is inactive, the second constituent must be the 
active one. 

Van Slyke has noted that the properties of clavin are almost 
identical with those of the isomorphous mixture of leucin and 
valin." The main difference is in its melting point. He cor- 
roborates Barger and Dale in proving the presence of leucin in 
clavin, but indicates the presence of valin, which these investigators 
had at first overlooked. Van Slyke ^" suggests that a mixture 
of leucin and valin should be tested physiologically. Shortly after 
Van Slyke's paper appeared, Barger and Dale reported the presence 
of valin in clavin along with asparaginic acid. It is interesting to 
note that Barger admits that some of the activity in ergot is due to 
iso-amylamin which may be derived from leucin. 

The evidence at present is against clavin being the active prin- 
ciple of ergot. Barger and Dale suspect that the activity of clavin 
is due to some admixed p. oxyphenylethylamin. 

Kraft has studied the ergot question and has proved that the 
bodies described by Robert and also those of Jacobj are not 
chemical individuals. He isolated two bases which he considered 
to be alkaloids. One of these is identical with the crystalline base 
of Tanret, so that Kraft retained the name of ergotinin which 
Tanret had originally used. According to Kraft its empirical 
formula is C35H39O5N5. The second base received the name hydro- 
ergotinin, as it was considered to be a hydrated form of ergotinin, 
therefore its formula would be C,.,5H4iN,,0„. These alkaloids were 
obtained from an ethereal extract by shaking it with a tartaric- 
acid solution, then freeing the bases with soda, again shaking 



Active Principle of Ergot. 



Am. Jour. Pharm. 
April, 1911. 



into ether and crystallizing from methyl alcohol. The two alkaloids 
were separated from one another by means of their sulphates. Ap- 
parently these bases could be transformed one into the other. Kraft 
also determined the presence of several lacton acids, secalonic acid 
and certain of its derivatives. As to whether these products are 
related to the crude scleroxantine of Dragendorff and Podwissotski 
is not considered. Kraft also found an oil, betain, cholin, mannit 
which had been noted by previous workers, Tanret's ergosterine 
and tri-methylamin which he believed were derived from betain. 
Walz had called attention to tri-methylamin in ergot, and Brieger 
in 1887 believed it traceable to cholin or isocholin. Kraft first used 
Keller's method of extracting the bases from ergot by means of 
alkaline ether, using MgO to secure alkalinity and to free them, 
but found that he could obtain these bodies by means of ether with- 
out adding the alkali and, therefore, argued that the alkaloids existed 
in a free condition, a suggestion which had been previously made 
by Keller. 

The physiological testing of these preparations was done by 
Jacquet. He tested the precipitate obtained from an ethereal ex- 
tract by means of petroleum ether. This precipitate would cor- 
respond to Jacob j's chrysotoxin. When administered as a powder, 
or an oily emulsion, to cocks it caused no bluing of the comb, but 
if dissolved with. NaOH, the filtrate, on injection into- cocks, pro- 
duced a bluing of the comb, and a similar injection into pregnant 
rabbits was followed by abortion. To produce this action in guinea 
pigs 0.25 gm. of the crude substance w^as required. This would 
really represent 50 gm. of ergot. 

After dissolving in glacial acetic acid and diluting with water, 
0.02 gram of ergotinin v^as injected into a pregnant guinea pig. 
This animal died in twenty-four hours with symptoms of ascending 
paralysis. There was no abortion. 

After dissolving in the same acid and lessening the acidity 
with NaOH, 0.013 gm. of hydroergotinine was injected into a cock. 
This injection was followed by a typical bluing of the comb, but 
the animal died the next day. A similar injection of o.oi gram of 
hydroergotinine caused bluing of the comb, but the animal did not 
die. An injection of the same amount of this base into a pregnant 
guinea pig caused convulsions. After two days 0.025 gm. more 
was injected into this animal. Twitchings of the muscles and rest- 
lessness were observed and four days later immature young were 



Am. Joyr. Pharm. ) 
April, 1911. / 



Active Principle of Ergot. 



163 



born. The injection of 0.04 gram of the hydroergotinine was made 
into a pregnant rabbit and two days later 0.05 gm. more given. On 
the third day this animal died of inflammation of the lungs and had 
not miscarried. 

A similar injection of even 0.25 gm. ergotinine caused no mis- 
carriage, but the animal died. Kraft, basing his conclusions on 
the experiments of Jacquet, says that the therapeutic use of ergot 
in exciting intense uterine contractions cannot be traced to the 
alkaloids, and that the alkaloids are convulsants, but that the 
bluing of the cock's comb may be due to hydroergotinin. However, 
Vahlen, who tested a sample of ergotinine sent by Kraft, found 
it practically non-toxic. The secalonic acids proved physiologically 
inactive. 

It must be confessed that considering the physiological data 
which Kraft presents, one would not feel convinced that these com- 
pounds represented the physiological activity of ergot, because 
while the pregnant rabbits aborted after the injection of hydro- 
ergotinin, yet these animals showed marked constitutional symp- 
toms, convulsions, etc., and it might be urged that abortion was 
only one feature of an intoxication. Again, by using glacial acetic 
acid and dilute alkalies as solvents for his bases, one is inclined 
to trace at least a portion of the action to decomposition products 
of the bodies brought about by such solvents. 

While Kraft was carrying on his work, independent investiga- 
, tions on the same subject were being pursued at the Wellcome 
Research Laboratory of London. The first paper on this subject 
from that institution was published by Barger,^^ Carr and Dale 
in 1906, shortly after Kraft's original paper appeared. These 
investigators isolated a crystalline base which they named ergotinin 
and assigned to it the empirical formula CggHg^^OgNg. It proved 
to be Tanret's crystalline base. This alkaloid formed amorphous 
salts and was found to be physiologically inactive, thus corroborat- 
ing the experiments of Kobert and Meulenhoff. They also isolated 
an amorphous base which they named ergotoxin. It was shown to 
have the composition Cs^H^^OcN,,. From it they succeeded in 
making a number of crystalline salts, especially an oxalate, hydro- 
chlorate, hydrobromate, and a phosphate. The free base, unlike 
ergotinine, was soluble in dilute sodium hydrate solution. They 
examined a sample of hydroergotinine sent by Kraft and found it 
to be identical with their ergotoxin. Vahlen claims, however, that 



164 



Active Principle of Ergot. 



Am. Jour. Pbarm. 
April, 1911. 



the toxicity of ergotoxin and hydroergotinin differed too much for 
them to be the same compound. Meulenhoff had a similar experi- 
ence but his experiments may be objected to on the ground that he 
was not using the purest products of these investigators. 

The intravenous injection of .0005 to .001 gram of ergotoxin 
into a pithed cat, under artificial respiration, caused persistent rise 
in the systemic blood pressure, without a preliminary fall. Dale 
noted that after such an injection adrenalin failed to cause an imme- 
diate rise in blood pressure and showed what he called a " reversal 
in action," that is, a fall in blood pressure. In doses of a few milli- 
grams, ergotoxin produced the typical bluing of the cock's comb and 
the uterine contractions in pregnant animals characteristic of ergot. 
The injection of 2 mg. of ergotoxin dissolved in dilute NaOH, into 
the ear vein of a rabbit, was followed in one case by dry gangrene 
of the ear. Unlike Robert's cornutine, it produced no convulsions 
in frogs. 

Barger and Dale at first believed, as did Kraft, that the 
active alkaloid was a hydrated form of the inactive one, and they 
adopted Kraft's view that each base could be converted into the 
other at will. The transformation of the inactive alkaloid into 
an active form was supposed to be accomplished by heating in dilute 
phosphoric acid. A more careful study has shown that this process 
does not yield ergotoxin phosphate, as was originally supposed, but 
a phosphate of ergotoxin-ethyl-ester. This has some physiological 
activity, so that in working with such solutions one is apt to be 
misled in attributing the action to this base. Ergotoxin thus con- 
tains a carboxyl group and the relation between the inactive and 
active alkaloids is that of a lacton. Barger and Dale believe the 
basic bodies isolated by Keller and also by Dragendorff to be mixtures 
of inert ergotinin with ergotoxin. 

They soon noted that all of the physiological activity of ergot 
could not be explained on the basis that ergotoxin was the sole 
active principle, but that there must be some water-soluble one 
to which most of the activity of ergot was due. In investigating the 
pressor action of putrid meat Barger and Walpole found it was due 
to p. oxyphenylethylamin, 

HO<ZZI>CH2CH2NH2, isoamylamin, ^^^^ >CH, CH^NHj, 

and phenylethylamin, and at once suspected some of these bodies 
to be the missing principles in ergot. They found p. oxypheny- 



Am. Jcmr. Pharm. 
April, 1911. 



} 



Active Principle of Ergot. 



165 



lethylamin, phenylethylamin and isoamylamin to be present in ergot. 
Para-oxyphenylethylamin can be shaken from water into ether pro- 
vided sodium carbonate is used, but not by means of NaOH'. Barger 
and Dale freed it as a benzoyl compound. The rise in blood 
pressure following the injection of ergot preparations was almost 
entirely due to the first constituent; the other two played only a 
subordinate role in the activity of ergot. They believed the first 
to be derived from tyrosin, while the others were traced to leucin 
and phenylalanin, respectively. Para-hydroxyphenylethylamin pro- 
duces a rise in blood pressure much like adrenalin, only weaker. 
This similarity in action might be expected from the close chemical 
relationship with adrenalin, which may be represented as 



Unlike adrenalin, this body is active when administered by mouth 
and produces no glycosuria. Isoamylamin and phenylethylamin 
have a similar action but less marked. Both compounds exert 
qualitatively the same kind of action on the true sympathetic 
system as adrenalin. Dale and Dixon say that " Both p. hydroxy- 
phenylamin and isoamylamin were found to cause contractions 
of the uterus and vagina of the rabbit in all functional conditions," 
and the injection of either base would bring on labor in pregnant 
animals. Like adrenalin, p. oxyphenylethylamin causes inhibition 
in the non-pregnant uterus of the cat, and causes contraction in 
the pregnant uterus, however, it is much less toxic. 

Kehrer noted that certain extracts of ergot produced an intense 
activity on the non-pregnant uterus of the cat, and that it was 
the dialyzed ergotin of Wernich which especially showed this 
action. This preparation is made by a slow process of dialysis, 
which suggested that it was due to the action of micro-organisms. 
The evidence at present points to ^-iminazoylethylamine as the 
compound to which this action is to be traced. This compound is 
derived from histidine by the elimination of carbon dioxide, in the 
same manner as p-hydroxyphenylethylamin is derived from tyrosine. 
Thus histidine 



HO 

H0< 



>CH(OH)CH2NHCH3. 



CH-NH 



\ 



CH-NH 



Vh+co, 




.CH 



II 

c 



CH^.CH.-NHj 



•i66 Active Principle of Ergot. { A^Xiaii^""' 

One month previous to the appearance of Barger and Dale's 
paper on /^-hnidazoylethylamine,'^ Kutscher had fractioned from 
ergot, by means of silver nitrate and ammonia, a derivative of 
histidin which was found to produce a marked fall in blood pres- 
sure in rabbits. He suspected it to be imidazoylethylamin, but 
found this latter would produce a rise in blood pressure while 
the base he obtained produced a fall and on this basis argued 
against its identity. The difference in the views of these investi- 
gators can be explained as due to differences in the animals used for 
testing their compounds. 

Recently another active principle has been found in ergot by 
Engeland and Kutscher. This has been found to be agmatine, a 
base which Kossel ^- found in herring roe. Agmatine is related to 
arginine in the same manner as /?-iminazoylethylamine is related to 
histidin. 

According to the latest view, the action of ergot in bluing 
the cock's comb is due to ergotoxine, while the blood pressure 
raising action is mainly due to p. oxyphenylethylamin, although 
ergotoxine plays a part in it. Parahydroplyphenylethylamine is 
difficult to isolate, and the amount present has not been determined 
chemically, but by physiological tests it is estimated that i kilogram 
of ergot will yield a few decigrams of this substance. 

The important problem now is whether ergotoxin, on decom- 
position, will yield these various pressor amines, and if not, are 
they all decomposition products of a common mother substance? 
Should this be so, this body remains to be isolated. 

Resume. 

Investigators have long recognized in ergot the presence of two 
bodies which have been designated as alkaloids. The specific 
alkaloid, ergotoxin, is present in such small quantities in ergot 
that we cannot trace the entire therapeutic action of ergot to 
this compound alone. It would be well to decide whether the 
action of ergotoxin is not really due to an amino group. The 
evidence at present points to the fact that ergot owes its activity 
to the presence of various basic amino compounds, and this is 
supported by the fact that only fresh ergot is official in certain 
pharmacopoeias, as it is known that ergot rapidly degenerates 
with the formation of tri-methylamine. It is interesting to note 



m. Jour. Pharm. ) 
: ;April, 1911. / 



Active Principle of Ergot. 



that practically every preparation introduced by chemists or 
pharmacologists has been endorsed by some clinicians as useful 
in labor. This may perhaps be explained on the basis that all 
such preparations have carried mechanically with them some of 
the active constituents of ergot, but the conditions under which labor 
pains intermit and recur are so little understood that it is rather 
difficult to always show the relation of ergot to such pains. 

A good review of this literature can be found in A. Bennecke. 
Der heutige Stand der Mutterkornfrage. Archiv. f. GyncckoL, 
vol. 38, p. 669, 1907. 

REFERENCES. 

^ Stearns, J. : Answer to Dr. Spalding's letter on ergot. New England 
Journal Med. and Surg., vol. 7, p. 216, 1818. 

^Journ. d. prakt. Heilkunde, vol. 45, pt. 5, p. 68, 1817. 
'Quoted by Orfila, P. Traite des poisons, vol. 2, p. 427, 1818. 

* Tessier. Mem. sur les effets du seigle ergote. Hist. Soc. Roy. de 
Med., Paris, 1777-78, vol. 2, p. 587, 1780; Memoire sur la maladie du 
seigle appellee ergot. Hist. Soc. Roy. de Med., 1776, Paris, vol. i, pt. 2, 
p. 417, 1779. Read. Traite du seigle ergote. Strasbourg, 1771. Vauquelin. 
Analyse du seigle ergote. Annal de chim. et de physique, vol. 3, p. 337, 1816. 
Pettenkofer. Chemische Versuche mit Mutterkorn. Repertorium f. Pharm., 
vol. 3, p. 65, 1817. Early historical details can be found in Wiggers' article. 

^ Wiggers, H. A. L. Untersuch. iiber das Mutterkorn. Ann. d. Pharm., 
vol. I, p. 129, 1832. 

* Mitscherlich, E. Ueber die Mycose, den Zucker d. Mutterkorns. 
Annal. d. Chemie, vol. 106, p. 15, 1858. 

' Czapek, F. Biochemie d. Pflanzen. vol. i, p. 231, 1905. 

'v. Schroff, C. D. Lehrb. d. Pharmakol., p. 617, 1873. 

" Wright, S. Observations on the oil contained in ergot of rye. Edin- 
burgh Med. and Surg. Journ., vol. 54, p. 51, 1840. 

^"Bonjean, J. Hist, du seigle ergote. Paris, 1842; Traite theorique 
et .pratique de I'ergot de seigle. Paris, 1845 ; Maurel, E. Determination 
des doses d'ergotine de Bonjean minima mortelles. Comp. rend. hebd. Soc. 
de Biol, vol. 54, p. 172, 1902. 

" Kohler, H. Vergleich. exper. Untersuch. iiber d. physiol. Wirkungen 
d. Ergotin; Archiv. f. path. Anat., vol. 60, p. 384, 1874; Rossbach, M. J. 
Einwirkung verschied. Mutterkornpraparate auf d. Herz. Verhandl. d. 
phys.-med. Gesellsch. in Wilrzburg, n. s. vol. 6, p. 19, 1874. 

^Hooker, C. On the properties and proximate principles of the ergot. 
Boston Med. & Surg. Journ., vol. 10, p. 298, 1834. 

Parola, L. Nuove richerche sperimentale sull'azione * * dello sprone 
dci graminacei. Ann. Univer. di Med., vol. 109, p. 241, 1844; vol. no, p. 
90, 1844. 



Active Principle of Ergot. 



( Am. Jour. Pharm. 
\ April, 1911. 



" Bertrand. Du seigle ergote et de son huile fixe. Journ. de Pharm. et 
Chilli., 3 s. vol. 19, p. 189, 185 1. 

Arnal. De Taction du seigle ergote. Bull, dc I'Acad. Roy. de Med., 
Paris, vol. 13, pt. i, p. 678, 1847-8. See also Pitat, J. A. Recherches sur 
la nature chimique de I'huile grasse retiree du seigle ergote. Dissert. Paris, 
1857. 

Winckler, F. L. Fortgesetzte Versuche u. Betrachtungen ueber Mut- 
terkorn und Propylamin. Jahrh. f. prakt. Pharm., vol. 25, p. 175, 1852; 
Briefliche Mittheil. ueber eine neue chem. Untersuch. d. Mutterkorns. Neues 
Rcpert. f. Pharm., vol. i, p. 22, 1852; Darstellung d. Propylamins aus 
Ergotin. Neues Repert. f. Pharm., vol. 23, p. 116, 1852; Ueber die 
Entstehung u'. d. chem. Constit. d. Mutterkorns. Jahrh. f. prakt. Pharm., 
vol. 26, p. 129, 1853. 

" Walz, G. F. Das fliichtige Alkaloid des Secale Cornutum. Jahrb. f. 
prakt. Pharm., vol. 24, p. 242, 1852; Neidhart, A. Zur Kenntniss d. 
wirksam. Bestandtheils d. Roggenmutterkorn. Neues Jahrb. f. Pharm., vol. 
18. p. 193, 1862. 

'^Ludwig, H. Chemisches iiber d. Mutterkorn. Archiv. d. Pharm., 
vol. 114, p. 193, 1863. 

'''Bley, L. F. Bericht. Archiv. d. Pharm., vol. 159, p. i, 1862. 

^ Wenzell, W. T. Essay on the active constituents of ergot of rye. 
Amer. Journ. Pharm., vol. 36, p. 193, 1864. See also Archiv. d. Pharm., 
vol. 200, p. 256, 1872 ; Ergoxanthein. Amer. Journ. Pharm., vol. 82, p. 410, 
1910. 

Herrmann, J. C. Beitr. z. chem. Kenntniss d. Mutterkorns. Neues 
Repert. f. Pharm., vol. 20, p. 283, 1871. 

Ganser, J. B. Untersuch. d. Bestandtheile d. Mutterkorns. Archiv. 
d. Pharm., vol. 194, p. 195, 1870. 

^ Manassewitz, T. Ueber d. wirksam. Bestandtheile d. Mutterkorns. 
Pharm. Zeits. f. Russland., vol. 6, p. 387, 1867. 

^*Haudelin, E. Beitr. z. Kennt. d. Mutterkorns. Dorpat. Diss., 1871. 
Blumberg, T. Beitrag z. Kenntniss d. Mutterkorn — Alkaloide. Dissert. 
Dorpat. 1878. 

Wernich, A. Beitrag z. Kenntniss d. Ergotinwirkungen. Arch. f. 
path. Anat., vol. 56, p. 505, 1872; Einige Versuchsreihen iiber das Mutter- 
korn. Beitr. 2. Geburtsch. u. Gyndkol., vol. 3, p. 71, 1874; Ueber eine 
geburtshilflich wichtige physiol. Nebenwirkung d. Mutterkorns. Cent. f. 
7ned. JVissens., vol. 11, p. 353, 1873; Ueber den wirksam. Bestandtheil d. 
Mutterkorns. Cent. f. ined. JVissens., vol. 11, p. 915, 1873; Salkowski, A.' 
Ueber d. wirksamen Bestandtheil d. Secale Cornutum. Berl. klin. Woch., 
vol. 13, p. 228, 1876. 

" Buchheim, R. Ueber d. wirksam. Bestandtheil d. Mutterkorns. Arch, 
f. exper. Path., vol. 3, p. i, 1874 ; Zur Verstandigung iiber d. wirksam. 
Bestandtheil d. Mutterkorns. Berl. klin. Woch., vol. 13, p. 309, 1876. 

^ Dragendorff and Podwissotsky. Ueber d. wirksam. Bestandtheile d. 
Mutterkorns. Arch. f. exper. Path., vol. 6, p. 153, 1877; Podwissotsky, V. 
Verbesserte Methode z. Darstellung d. Sclerotinsiiure. Pharm. Zeits. f. 
Russland, vol. 22, p. 393, 1883. 



"^"'ApXim*"" } Active Principle of Ergot. 169 

Ganguillet, F. Untersuch. ueber d. Wirkung. d. Sclerotinsaure auf 
d. puerperal. Uterus. Archw f. Gyndkol, vol. 16, p. 174, 1880. 

^"Rennert, Zur Wirkung d. Sklerotinsaure auf. d. Menschen. Cent, 
f. GyfKBkol, vol. 4, p. 513, 1880. 

^Nikitin, W. Ueber d. physiol. Wirkunk * * Sclerotinsaure. Ver- 
handl. d. phys. med. Gesells. in Wurzhurg. n. s. vol. 13, p. 143, 1879. 

^Zweifel, Ueber d. Secale Cornutum. Arch. f. exper. Path., vol. 4, p. 
387, 1875. 

^^Denzel, J. Secale cornutum. Archiv d. Pharm., vol. 222, p. 49, 1884. 

^*Mauk, H. Ein neues Mutterkorn-extract. Dissert. Tiibingen, 1884. 
Tanret, C. Sur la presence d'un nouvel alcaloide, I'ergotinine, dans 
le seigle ergote. Comp. rend., vol. 81, p. 896, 1875 ; Sur I'ergotinine, 
alcaloide du seigle ergote. Comp. rend., vol. 86, p. 888, 1878 ; De I'ergotinine. 
Ann. de chim. et de phys., 5 s. vol. 17, p. 493, 1879; L'ergotinine crystallisee. 
Bull, de I' Acad, de med., vol. 34, p. 919; Sur I'ergotinine. Bull. gen. de 
Ther., vol. 106, p. 418, 1884; Sur les principes actifs du seigle ergote. 
Bull. Sci. de Ther., vol. 18, p. 228, 1885 ; Sur un nouveau principe immedat. 
de I'ergot de seigle, I'ergosterine. Journ. de pharm. et de chim., 5 s. vol. 
29, p. 225, 1889; Sur une base nouvelle retiree du seigle ergote. Annal. 
de Chimie et de Phys., 8 s. vol. 18, p. 114, 1909. 

^^Ludwig, H. Vorkommen von Cholesterin im Mutterkorn. Archiv d. 
Pharm., vol. 187, p. 36, 1869. 

^ Robert, R. Ueber Mutterkornpraparate. Cent. f. GyncFkol, vol. 10, 
p. 307, 1886. 

^*Eulenburg, A. Subcutane Injectionen von Ergotinin. Deutsch. mcd. 
Woch, vol. 9, p. 637, 1883. 

Galippe and Budin. Sur Taction de I'ergotinine. Gas. med. de Paris, 
4 s. vol. 7, p. 150, 1878. 

Chahbazian, C. Du traitement des hemorrhages uterines post-partum. 
Archiv. de tocologie, vol. 10, p. 449, 1883. 

"Robert, R. Ueber d. Bestandtheile u. Wirkungen d. Mutterkorns. 
Arch. f. exper. Path., vol. 18, p. 316, 1884; Rruskal, N. Ueber d. Zusammens- 
etzung d. Ergotinsaure. Arb. d. pharm. Institut z. Dorpat., vol. 8, p. 170, 1892; 
Bombelon, E. Ergotinin u. Cornutin. Pharm. Zeit., vol. 33, p. 109, 1888. 

^ Griinfeld, A. Beitr. z. Rennt. d. Mutterkornwirkung. Arh. d. pharma- 
kol. Institut 2. Dorpat., vol. 8, p. 108, 1892. 
Robert, R. Ibid, p. 369- 

Robert, R. Ueber Mutterkornpraparate. Cent. f. Gyncekol., vol. 10, 
p. 306, 1886. 

Robert, R. Present State of the Ergot Question. Practitioner, vol. 35, 
p. 414, 1885. 

*^ Cornutin was obtained by extracting ergot with 3 per cent. HCl, then 
neutralizing with Na2C03, evaporating and extracting with alcohol. The 
alcohol was distilled off and the residue made alkaline with NaaCOs and 
then shaken with acetic ether. The cornutin with other alkaloids was 
then shaken into water containing citric acid. 

*^ Erhard, Ueber d. Wirkung des Cornutin. Cent. f. Gyncekol., vol. 10, 
p. 309, 1886; Rrohl, P. Rlin, Beobachtungen ueber d. Einwirkung einzelner 
Mutterkornpraparate. Archiv. f. Gyncekol, vol. 45, p. 43, 1894; Thomson, H. 



Active Principle of Ergot. 



f Am. Jour. Pharm. 
1 April, 1911. 



Klin. Erfahrangen iieber d. Cornutin in d. Geburtshilfe u. Gynjiekol. Cent, 
f. Gyncckol., vol. 13, p. 172, 1889; Ueberschaer, E. Klin. Beitr. z. Anwend. 
d. Cornutin. Diss. Breslau, 1897 ; Meisels, W. A. Das Cornutin als 
wirksames blutstillendes Mittel bei Blutungen d. Harn-u. Geschlechtsorgane. 
Pest. Med.-chiin. Presse, vol. 27, p. 921, 1891 ; Levitski, L. Material z. 
Frage ueber d. Pharmakol. d. Cornutins., St. Petersburg, 1887. Diss. 
(Seen only in reference.) 

Griinfeld, A. Zur Kenntniss d. Sphacelinsaurewirkungen. Arbeit, a. d. 
pharm. Institut z. Dorpat., vol. 11-12, 1895. 

■'^Ludwig, H., and Savor, R. Zur Wirksamkeit d. Cornutins. Wien. 
klin. Woch., 1895, vol. 8, pp. 395, 420. Note. Fluid preparations undergo de- 
composition partly owing to micro-organisms. Leopold, H. Ueber das 
Vorkommen von mikroorganismen in Ergotinlosung. Diss. Wiirzburg, 
1887. 

^"Tanret, C. Cornutine et ergotinine. /. Pharm. et Chim., 5 s, vol. 11, 
p. 309, 1885. 

Griinfeld, A. Beitr. z. Kennt. d. Mutterkornwirkung. Arbeit d. 
Pharmakol. Institut z. Dorpat., vol. 8, p. 108, 1892; Zur Kenntniss d. 
Sphacelinsaurwirkungen. Dorpat- Arbeit., vol. 11-12, 1895. 

Keller, C. C. Ueber d. Werthsbestim. von Droguen u. galenisch. 
Preparate. Schweiz. Woch. f. Chem. u. Pharm., vol. 32, pp. 121, 133, 1894. 
Neue Studien iiber Secale cornutum- Schweiz. Woch. f. Chem. et Pharm., 
vol. 34, p. 65, 1896. 

See also Caesar and Loretz, Hendelsbericht, 1894, p. 49. 
^* Caesar and Loretz. Geschaftsberichte, p. 55, 1902. Dohme, A.R.L. 
Assay of Ergot. Proc. Amer. Pharm. Assoc., vol. 43, p. 263, 1895. 

Santesson, C. G. Ueber die Wirkung des Cornutins. Keller. Skan. 
Archiv. f. Physiol., vol. 13, p. 107, 1902. 

^ Palm, H. Untersuch, iiber d- Bedeutung d. Mutterkorns u. seiner 
Preparate f. d. Geburtshiilfe. Archiv. f. Gyncekol., vol. 67, p. 674, 1902. 

Bischofberger, A. Geburts.-klin. Untersuch. u. d. Haltbarkeit d. Mut- 
terkorns. Diss. Bern., 1897. 

Santesson, p. 108. 

By a strange misunderstanding it was once proposed to extract the 
oil from ergot with ether as a method of preserving indefinitely the 
activity of the ergot. Riviere de la conservation indefinite de la poudre 
de siegle ergote. Bull, de la Soc. Med. de I'Yonne, vol. 28, p. 89, 1888. 

For some data as to the value of ergots at various ages, see Pottiez, C. 
Notes complements a I'etude chim. du seigle ergote. Journ. de pharm., 
vol. 54, pp. 121, 161, 1898. 

''Dohme, A. R. L., and Crawford, A. C. The Active Principle of 
Ergot. Proc. Amer. Pharm. Assoc., vol. 74, p. 503, 1902. 

^° Schaerges, O. Ueber Secornin (Ergotin Keller) u. d. wirksamen 
Bestandtheile des Mutterkorns. Pharm. Centralh., vol. 46, p. 789, 1905 ; 
Barger, G., and Dale, H. H. Ergotoxine and some other Constituents of 
Ergot. Biochemical Journ., vol. 2, p. 277, 1907. 

^^Jacobj, C. Sphacelotoxin. Arch. f. exper. Path., vol. 39, p. 85, 1897. 

*'^Zeeh, H. Weit. Beitr. z. chem. Kennt. einiger Bestandtheile au's Secale 
Cornutum Dissert. 1894. Jena. 



Am. Jour. Pharm. 1 
April, 1911. J 



Active Principle of Ergot. 



171 



®^ Meulenhoff, J. L. Nederl. Maatsch. ter hevornd den Pharmacie, vol. 8, 
1899. (Seen only in reference.) 

®* Rielander. Einige neue Bestandtheile des Extraktum Secale cornuti. 
Gesellsch. z. Befdrd. d. gesamt. Naturw., 1908, p. 173, 1909. 

Ludwig, H. Chemisches ueber d. Mutterkorn. Archiv d. Pharm., 
vol. 164, p. 193, 1683. 

®®Vahlen, E. Clavin, ein neuer Mutterkornbestandtheil. Archiv. f. exper. 
Path., vol. 55, p. 131, 1906; Ueber einen neuen, wirksam., wasserloslich. 
Bestandteil des Mutterkorns. Deutsch. med. Woch., 1905. 

VanSlyke, D. D. Clavin. Journ. of Pharmacol., vol. i, p. 265, 1909. 

®* Kraft, F. Ueber das Mutterkorn. Archiv. d. Pharm., vol. 244, p. 336, 
1906; Krystallisirtes Hydroergotinsulfat. Archiv. der Pharm., vol. 245, p. 
644, 1907. 

Brieger, L. Die Quelle des Trimethylamins in Mutterkorn. Zeits. 
f. physiol. Chemie, vol. 11, p. 184, 1887. 

Barger, G., Carr, F. H., and Dale, H. H. An active alkaloid from 
ergot. Brit. Med. Journ., 1906, vol. 2, p- 1792. Barger, G., and Carr, F. H. 
Note on ergot alkaloids. Pharm. Journ., 1906. Barger, G., and Carr, F. 
H. The alkaloids of ergot- Journ. Chem. Soc, 1907, vol. 91, p. 337. Barger. 
G., and Ewins, A. J, Alkaloids of ergot. Journ. Chem. Soc, vol. 
97~9^, P- 284, 1910. Dale, H. H. On some physiological actions of ergot. 
Journ. of Physiol., vol. 34, p. 163, 1905. Barger, G., and Walpole, 
G. S. Isolation of the pressor principles of putrid meat. Journ. of Physiol., 
vol. 38, p. 343, 1909. Dale, H. H., and Dixon, W. E. The action of pressor 
amines produced by putrefraction. Journ. of Physiol., vol. 39, p. 25, 1909. 
Barger, G. De Nieuwste Onderzoekingen over Moederkoorn. Pharm. 
Weekhlad, No. 14, 1910, p. 347- Barger, G., and Dale, H. H. Water- 
soluble active principle of ergot. Proc. Physiol. Soc, p. 77, 1909. Walpole, 
G. S. Syntheses of p. hydroxyphenylethylalkylamines. Journ. Chem. Soc, 
vol. 97-98, p. 941, 1910. Barger, G., and Dale, H. H. A third active 
principle in ergot extracts. Proc Chem. Soc, vol. 26, p. 128, 1910; Presence 
in ergot * * of /3-imidazoylethylamine. Journ. of Physiol, vol. 40, p. 00, 
1910. Barger, G., and Dale, H. H. Ergotoxine. Journ. of Physiol. Bio- 
Chem. Journ., vol. 2, p. 240, 1907- Barger, G., and Dale, H. H. /3-iminazoyl- 
lethylamine a depressor constituent of intestinal mucosa. Journ. of Physiol, 
vol. 41; p. 499, 1911. Barger, G., and Dale, H. H. 4-^-Amincethylglyoxaline 
and the other active principles of ergot. Journ. Chem- Soc, vol. 97-8, p. 
2592, 1910. Chemical structure and sympathomimetic action of amines- 
Journ. of Physiol, vol. 41, p. 19, 1910. Dale, H.H., and Laidlaw, P. P. 
Physiological action of ^-iminazoylethylamine. Journ. of Physiol, vol. 41, 
p. 318, 1910. Barger, G. Isolation and synthesis of p-hydroxyphenylethyl- 
amine. Journ. Chem. Soc, vol. 95, p. 1123, 1909. Barger, G., and Walpole, 
G- S. Further syntheses of p. hydroxyphenylethylamine. Trans. Chem. Soc , 
vol. 95, p. 1720, 1909. 

Kutscher, F. Die Physiol. Wirkung einer Secalebase. Zeit. f. Physiol., 
vol- 24, p. 163, 1910. Engeland, R., and Kutscher, F. Ueber eine zweite 
wirksame Secalebase. Zent. f. Physiol, vol. 24, p. 479, 1910. 

^^Kossel, A. Ueber das Agmatin. Zeits. f. Physiol. Chem.^ vol. 66, p. 
257, 1910. 



tJ2 



Keeping Qualities of Ergot. 



Am. Jour. Phaini. 
April, lyil. 



THE KEEPING QUALITIES OF ERGOT AND ITS FLUID 

EXTRACTS. 

By Horatio C. Wood, Jr., 
Professor of Pharmacology and Therapeutics in the Medico- 
Chirurgical College. 

Drugs are the doctor's tools. If a carpenter's tools are of poor 
steel, they will not take a fine edge, and cut but slowly; in ordinary 
work, with soft wood, the carpenter can manage to make some 
progress, even with comparatively poor tools, but when an extra 
hard piece of timber must be worked the edge of the soft steel will 
turn, and the tool will no longer cut at all. In an analagous way the 
physician under ordinary conditions, in the less serious complaints, 
may make some sort of progress even with drugs of inferior quality, 
but in an emergency, when life is perhaps hanging in the balance, it 
is essential that he have remedies on whose potency he can rely. 
Ergot is among those drugs which are frequently employed in con- 
ditions of immediate danger, and if pharm_acy is to be a true hand- 
maiden of medicine she must use her utmost endeavor tO' supply the 
physician with reliable preparations of ergot. 

It has long been known that crude ergot was liable to deterior- 
ation. The United States Pharmacopoeia says " after being kept 
more than one year it is unfit for use." While this statement is a 
proper recognition of the instability of the drug, as a legal standard 
it is a little extreme. Under present commercial conditions it is 
often impossible to obtain ergot which conforms strictly to the United 
States Pharmacopoeia. The ergot crop is harvested chiefly during 
the month of August, and after collection, the bulk of the crop is sent 
to the large English exporters from whom it is imported into this 
country, and usually does not appear upon the American market until 
about January. It is, therefore, very evident that any ergot which is 
bought between the months of August and January must be more 
than one year old. Under the most favorable conditions, therefore, 
during only seven months of the year can the pharmacist possibly 
obtain ergot which is strictly U.S. P. Moreover, he has no 
means of being sure than the jobber from whom he buys his 
ergot is supplying him with the latest crop. There is reason 
to believe that some importing houses in New York keep their ergot, 
if not disposed of, for several years, I have had in my possession a 



Am;' Jour. Pharni. ) 
April, 1911. / 



Keeping Qualities of Ergot. 



173 



sample of crude ergot which was obtained from a large London im- 
porter accompanied with the statement that they had had it for three 
years and that they obtained it in turn from a New York firm who, 
to their certain knowledge, had had it for at least four years, and 
when we remember that the New York firm must have imported the 
ergot from Europe, so that it was at least one or two years old when 
they got it, it is evident that this sample of ergot was nearly, if not 
quite, ten years old. The specimen consisted largely of granular 
detritis, evidence of the ravages of insects, and the letter, comment- 
ing upon the appearance of it, stated with a delicious naivete : 
" If sifted it would look presentable, but could be saleable at current 
prices only if a scarcity came along, or if wanted for a cutting con- 
tract for some institution ! " 

Sad as it is to contemplate this disregard of our national standard, 
it becomes horrifying when we consider the justness of that standard, 
and remember the uses to which the drug is put. Griinfeld obtained 
a freshly gathered sample of ergot which he tested at various inter- 
vals during a year. He found that in October it required twice the 
dose to produce the coxcomb reaction that it did when gathered in 
August, that by February it required eight times the dose, and by 
June no dose would produce the characteristic effect. He does not 
state definitely what precautions were observed in keeping the ergot, 
and my own experience would lead me to believe with proper care 
crude ergot can be preserved more successfully than in his experi- 
ments. His work shows, howevei", 'the absolute necessity of using as 
fresh ergot as can be obtained. 

There are two causes for the loss of activity in ergot :■ ( i ) the 
attacks of insects, and (2) chemical change taking place in its 
active principles. In regard to the first, there is at present no positive 
evidence that, if the ergot is sifted, the whole grains which are left 
upon the sieve are inferior in quahty' to ordinary' ergot. Moreover, 
it is comparatively simple to protect the drug against these enemies. 
A little chloroform vapor is all that is necessary. 

Concerning the change which takes place in the active principles 
of the drug, we have little information as to the chemical nature of 
these alterations or how to prevent them. Basing my conclusions 
upon the results of a single experiment, I have advised .that 
powdered ergot should be dried for 48 hours at a temperature of 37° 
C. and then hermetically sealed, a little chloi-oform being previously 
added to prevent the growth of any mites. 



174 



Keeping Qualities of Ergot. 



(Am. Jour, riiarm. 
\ April, 1911. 



It is a common belief among pharmacists that the fluid extract 
of ergot is much more permanent than the drug itself, but a series 
of experiments which were carried out by Dr. Hofer and myself has 
convinced me that it is a preparation which cannot be kept indefi- 
nitely. Whether it deteriorates more rapidly or less rapidly than the 
drug itself, I am not prepared to state, but I am satisfied that a fluid 
extract should not be kept more than a year under any conditions. 

We investigated the problem of the influences which tended to 
hasten undesirable changes in the fluid extract of ergot in the follow- 
ing manner : Each sample of fluid extract of ergot as it was received 
from the maker was divided into three portions, one of which was 
immediately placed in an amber colored bottle which was com- 
pletely filled so as to exclude any air, and hermetically sealed. The 
second portion was placed in a wide-mouthed container which was 
simply stoppered with cotton so as to keep out the dust, in this 
manner allowing free exposure to atmospheric influences, alcohol 
being added from time to time as it evaporated from the fluid 
extract. The third portion was kept in the bottle in which it was 
received from which, from time to time, small amounts would be 
removed for experimental purposes, the cork being replaced each 
time, in this way closely simulating the conditions in the ordinary 
pharmacy. It may be noted that these bottles were kept at room 
temperature and many of them through the summer. The follow- 
ing table shows the average loss per week of sphacelotoxin when 
assayed by the method described by me. (American Journal of 
Pharmacy, May, 1909, page 215.) 

I have included also the figures obtained by Griinfeld for crude 
ergot. As we found that the rate of deterioration was not constant, 
I have divided the table into two portions, the first of which gives 
the average loss of all the samples which were kept for from five to 
fifteen weeks, and the second, those which were kept sixteen to 
twenty-five weeks. 



5-15 weeks 



16-25 weeks 



Open 
Corked 
Sealed 
Griinfeld 



6.4% loss per week 



2.5% loss per week 
1.5% " " " 

1.3% " " " 
3-5% " " " 



2.6% 
1.6% 
6.2% 



In the paper published by Doctor Hofer and myself {Archives 
of Internal Medicine, October, 1910, page 388), we have brought 



Am. Jour. Pharm. » 
April, 1911. f 



Keeping Qualities of Ergot. 



175 



forward evidence which served to convince us of the reUabiUty of this 
process of chemical assay. It is to be noted, however, that my con- 
clusions concerning the deterioration of the fluid extract of ergot are 
not based purely upon this chemical evidence, but also upon a 
number of physiological tests. We have found that the loss of 
activity as measured by its power to raise the blood pressure occurred 
more or less harmoniously with the figures just quoted, although we 
have only four samples concerning which we have complete records 
of the rapidity of change in physiological power under varying 
conditions. 

As to the details of keeping, I may say that with the exception 
of the sealed bottles, which were invariably of amber-colored glass, 
no effort was made to protect the drug against the effects of the 
light, as we wished, in the one instance, tO' imitate, as nearly as pos- 
sible, conditions in the retail pharmacy, and in the other instance, 
to see how rapidly the fluid extract would lose strength under the 
most favorable conditions for such change. 

There are prominent obstetricians who maintain that ergot is an 
inert drug, so unfortunate has been their experience with its use. 
It is manifest that the poor quality of ergot upon the market is 
robbing the medical profession of a very valuable tool, and endanger- 
ing the lives of those patients whose physicians place too much 
confidence in this drug. There is, therefore, crying need for correc- 
tion of this really horrible state of affairs. In view of the fact that 
there is still much difference of opinion as to the best methods of 
testing the activity of ergot, and also of the fact that none of these 
methods can be satisfactorily conducted by retail pharmacists, — 
while the method of chemical assay suggested by myself is simple 
enough for any pharmacist to carry out, modesty forbids me 
urging it as a universal test until its value has been confirmed by 
other observers, — it is essential that pharmacists do what they can 
to see that their fluid extract at least fully represents the crude 
drug from which it was manufactured. For this reason, I would 
vigorously urge : ( i ) that the fluid extract of ergot be marketed by 
wholesalers in packages of not over four fluid ounces, and immedi- 
ately after the completion of the percolation; (2) thsit each bottle carrv 
plainly upon the label the date of its manufacture 1(3) that no phar- 
macist be permitted to dispense a fluid extract of ergot which is more 
than six months old. 



17.6 



The Response of Gums. 



j Am. Jour, Pharni. 
t April, 1911. 



THE RESPONSE OF GUMS AND SIMILAR SUBSTANCES 
TO MOORE'S REACTION. 

By Torald Sollmann 
From the Pharmacological Laboratory of Western Reserve University, 

Cleveland, Ohio. 

The well-known reaction of Moore or Heller consists in the 
occurrence of a yellow to dark brown color, when glucose solution 
is heated with KOH or NaOH. The reaction also occurs at ordin- 
ary temperature, but much more slowly. 

This test, which was introduced in 1844 by John Moore ^ and 
F. Heller, has been practically displaced by other sugar-tests. It 
is especially unreliable for small traces of sugar in colored fluids. 
In urine, for instance, Rosenfeld (Deutsche medicin Wochenschrift, 
1888, p. 451) failed to obtain reliable results even with 0.5 per cent, 
of glucose. In a pure solution, the test is very much more delicate. 
In my hands, even o.oi per cent, of glucose gave a faint yellow 
color, which, however, bleached almost completely in twenty-four 
hours. A 2 per cent, solution of glucose gave a mahogany color, 
which was not noticeably changed in twenty-four hours. 

The depth of color is also determined by the amount of free 
alkali. Framm (quoted from Neubauer and Vogel, Analyse des 
Harnes, tenth edition, p. 100), found that o.oi per cent, of dextrose 
gave a good reaction with 0.5 per cent, NaOH. With sodium 
carbonate I found only a slight degree of darkening. 

The nature of the reaction and of the products formed by the 
decomposition of the sugar are not clearly understood, although 
they have been the subjects of careful investigation {Cf. Neu- 
bauer & Vogel, I.e.) ; the process is evidently complex, and probably 
varies with the conditions, and with the nature of the substances 
employed. 

Aside from dextrose, the test gives positive results with many 
other carbohydrates. According to Neubauer & Vogel (/. r, ) and 
Hammarsten (Lehrbuch dcr Physiologischcn Chcinie), it is given 

^ I may take this occasion to correct some curious errors in citations of 
Moore's original paper. Neubauer and Vogel, and Marck's Reagentien 
Verzeichniss both give a wrong reference, namely The Lancet, ii, Sept. 26, 
1844; after considerable search we located it in The Lancet, ii, Sept. 14, 1844, 
p. 751; even the index of The Lancet gives the wrong page (75) ! 



Am. Jour. Pharm. ) 
April, 1911. j 



The Response of Gums. 



177 



by the pentoses (xylose) and hexoses (dextrose, levulose) ; of the 
disac char ides, maltose and lactose give the reaction, but not sac- 
charose. Mucin is also said to respond positive. Of the polysac- 
charides, glycogen and dextrin are practically negative, but may 
react after prolonged heating, which presumably decomposes them. 
Starch is negative; so also is inosit. 

All aldehydes which I have tried react positive (acetaldehyde, 
paraldehyde, formaldehyde, benzaldehyde and cinnamic aldehyde). 

In all the preceding instances, the substances which give positive 
results reduce Fehling's solution, and those which react negatively 
to Moore's test also fail to reduce the copper. 

On applying these tests to a number of gums and similar sub- 
stances, I found a somewhat different behavior, which I have not 
seen recorded: These gums {acacia, tragacanth, and cherry gum), 
as also, agar, cetraria, and chondriis, give a golden or brownish- 
yellow color on heating with sodium hydroxide solution ; but they 
do not reduce Fehling's solution even on prolonged heating. 

As many of these may contain reducing sugar, they must be 
thoroughly washed (sometimes for several days). Even then there 
might be a suspicion that Moore's test is more delicate than Fehl- 
ing's, but I have convinced myself that a dextrose solution which 
gives the Moore's test much more faintly than the agar solution, 
nevertheless gives a very plain precipitate with Fehling's test. With 
the difficulty soluble gums, the Moore's reaction can be best observed 
by heating the soaked substance directly with the reagent. I have 
appHed the same technic to the Fehling's test, using one part of 
Solution A to three parts of Solution B. The results were nega- 
tive, except with occasional specimens, which were presumably not 
sufficiently washed. 

In the case of cetraria and cherry gum, the Moore's reaction was 
applied separately to the portions soluble and insoluble in water. 
The insoluble residue gave negative results. Cornstarch and 
glycogen did not give the Moore's reaction. 

After heating with dilute acids (which converts gums into 
hexoses and dextroses) all these substances reduced the Fehling's 
solution. 



178 



Medicated Gauzes. 



{Am. Jour. PharmJ 
April, 1911, 



THE EXTEMPORANEOUS PREPARATION OF 
MEDICATED GAUZES. 

By George M. Beringer, Jr., P. D. 

A few years ago the writer was called upon to prepare iodoform 
gauze bandages for an emergency order. This led to an examina- 
tion of the literature upon the subject and experimentation upon 
improved methods for the preparation of such gauzes as are in 
common use. The results of the investigation are presented in this 
paper. 

The earliest type of antiseptic gauze was that of Lister, made 
by soaking the material in a melted mixture of resin, paraffin and 
phenol. It is needless to say that such a ' ' messy " preparation as 
this has long since passed from the American market. Many recent 
foreign works, and a few of our own, however, still retain the for- 
mula. Some, also, give a similar formula for the preparation of 
iodoform gauze, and the common method practised to-day is to 
distribute the iodoform over the surface of the gauze in the form of 
a starch paste suspension with glycerin. While this is better than 
the resin method, I believe that, aside from the required antiseptic, 
the less foreign material contained in a surgical dressing the better. 
Such material not only lessens the absorbent qualities, but may be 
irritant and, surely, restrains the activity of any antiseptic with 
which it may be combined. 

Another point worthy of note is the incompleteness of many of 
the published formulas. One authority gives a formula for bichlo- 
ride gauze. The amount of liquid directed for impregnation is 
one fluid ounce and contains 2 grains of mercuric chloride. No 
amount of gauze is specified. If the resulting preparation is to be 
of the usual i to 1000 strength, about 2000 grains of gauze will 
be required. The amount of liquid directed will hardly perceptibly 
moisten this, yet the directions are " Immerse for twelve hours " — 
" Wring out " and Allow to dry as far as the glycerin will permit." 

The first rational method appears to have been proposed by 
H. Helbing in 1889. He recommended ether or a mixture of ether 
and alcohol for the preparation of an extended list of gauzes. This 
was ideal in so far as no foreign material remained in the finished 
product, but the cost of the solvent, the danger from fire, and the 
unpleasant effects upon the operator precluded any extended com- 



Am. Jour, Pharm. 1 
April, 1911. / 



Medicated Causes. 



179 



mercial application. However, in recent years, the reduced cost of 
ether and other solvents and the improvement of mechanical appli- 
ances for manipulation should have caused a general adoption of the 
method, but it seems to have been overlooked. 

In the case of the iodoform gauze bandages first mentioned, 
ether was tried, but had to be abandoned, because of fire risk and 
its effects upon the operator. A solvent similar in diffusive proper- 
ties to ether was sought and found in acetone. The tightly rolled 
bandages were saturated to the core in a few minutes after pouring 
the solution upon them. Furthermore, they dried perfectly and 
evenly as fast as they could be rewound. The same method has 
been applied to a number of other gauzes with equal success. The 
vapors do not seem to have any ill effect upon the operator. 

When one remembers how long the name absorbent gauze has 
been used, it seems strange that a method of preparation based 
entirely upon the absorbent qualities has not been more generally 
used. Yet the majority of the published formulas direct an excess 
of liquid to be applied and subsequently removed by expressing to 
a given weight, and drying, losing sight of the fact that an amount 
of liquid just short of saturating the material would quickly and 
evenly diffuse, and evenly distribute the medicament. The appli- 
cation of this principle prevents the uneven distribution of the 
medicament as caused by the evaporation of a large amount of 
liquid, when heavy and slowly volatile from the lower, or when 
light and quickly volatile from the upper portions of the material 
suspended for drying. Obviously, it would have the added advan- 
tage of lessening the exposure of the product to septic contamina- 
tion, as well as that of bringing it into the class of extemporaneous 
preparations by the saving in time effected. 

Before proceeding with the individual formulas, it might be well 
to describe the gauze used and the necessary precautions to secure 
asepsis, even though they present nothing new. The older directions 
required the removal of the resins and fats from the gauze by solu- 
tions of soda or potassa and its bleaching by chlorinated lime or 
soda. It was then directed to be washed with hydrochloric acid 
and finally with water. Suitable material can now be had, already 
prepared, in the market. A satisfactory product contains about 
twelve threads to the centimetre both on the woof and on the warp, 
and is conveniently used in widths of about 90 cm. (i yd.). One 
metre of this weighs about 25 Gms. It should be free from 



i8o Medicated Ganges. (Am jour I'baini. 

( April, 1911. 

chlorine and starch or guin-Uke material. According to the British 
Pharmaceutical Codex, i Gramme, when incinerated, should yield 
" practically no residue." 

It is safer to prevent contamination, as far as possible, than to 
depend entirely upon sterilization for an aseptic product. The 
tables, floor and all other possible portions of the room where 
gauzes are to be prepared should be scrubbed with hot lye solution 
containing phenol. The top of the work table should be preferably 
of glass, but, if not, should be thoroughly scrubbed and finally 
washed with a 1-500 bichloride solution," and covered with sheets 
of sterilized parchment paper before any dressings are placed upon 
it. The hands and nails of the operator should be scrupulously 
clean and washed, just before handling the material, in a 5 per cent, 
phenol solution. The clothing and hair should be covered with 
garments or wrappings of sterile muslin or gauze. Also, any 
objects not capable of being moved from the neighborhood of the 
work, and not needed for it, should be covered with sterile cloths. 
Jars, rods and all other materials should be sterilized where pos- 
sible by boiling in water for fifteen minutes. Cartons and paper 
for packing and wrapping should be heated in an oven for one-half 
hour at a temperature of i20°-i5o° C. 

The gauzes on the market, both plain and medicated, are in 
two forms — moist and dry. Hence directions for both are given. 
The moist forms seem to have the preference of most surgeons. 
They are more readily sterilized in that condition, are more pliable 
and suitable for packing wounds and cavities, insure more rapid 
drainage, and have less tendency to adhere to the wound surfaces. 

Plain Absorbent Gauze, Dry. 

The gauze should be cut into convenient lengths and rolled or 
folded into suitable bundles, wrapped in sterilized parchment paper 
and placed in a steam bath for one half-hour. It should then be 
removed and placed in previously sterilized cartons or wrapped in 
sterilized tough, heavy paper. 

Plain Absorbent Gauze, Moist. 

The gauze should be cut into suitable lengths, then sprinkled with 
sterilized distilled water containing 5 per cent, of glycerin and 
packed in previously sterilized amber glass jars. The filled jars, 



Acu, Jour. Pbarnj. I 
Apiil, 1911. / 



Medicated Gauges. 



i8i 



with the caps loosely placed, should then be resterilized in a steam 
bath for one half-hour, after which they should be immediately 
sealed. 



Dissolve the iodoform in the acetone and pour over the gauze 
loosely placed in a sterilized jar, or other suitable container, fitted 
with a close cover. Cover and allow to stand about fifteen minutes 
or until evenly moistened. Remove from the jar and drive off 
the acetone by waving in the air. Immediately wrap in sterilized 
parchment paper. Resterilize in steam bath for fifteen minutes and 
then enclose in a tight carton, or tough paper wrapper, previously 
steriHzed. 



Prepare by taking iodoform gauze dry, as above, and sprinkling 
with freshly sterilized distilled water containing 5 per cent, of 
glycerin (about 75 c.c. wif be needed for each 100 Gm. of gauze). 
Allow to stand in a covered sterile jar till the moisture is evenly 
distributed. Pack into sterilized amber glass jars and resterilize, 
with lids of jars loosely placed, in a steam bath for fifteen minutes. 
Hermetically seal the jars immediately upon removal from the 
sterilizer. 

Resterilization for only fifteen minutes is directed for iodoform 
gauze because of the ease with which iodoform is decomposed by 
heat. 

Prepared in this manner, the iodoform is sO' firmly attached 
to the gauze that very little is washed off when immersed in water. 
With the starch paste suspension method, as previously mentioned, 
the secretion from a freely discharging wound, or the condensed 
steam from sterilization is sufiicient to flush it from the material. 



Iodoform Gauze, 10 Per Cent., Dry. 



Iodoform .. . 
Acetone . . . . 
Sterile gauze 



10 Gm. 
100 c.c. 
100 Gm. 



Iodoform Gauze, 10 Per Cent., Moist. 



Thymol Iodide Gauze, 5 Per Cent., Dry. 



Thymol iodide 
Chloroform . . 

Acetone 

Sterile gauze 



5 Gm. 
25 c.c. 
50 c.c. 
100 Gm. 



l82 



Medicated Gauzes. 



J Am, Jour. Pharm. 
1 April, 1911. 



Dissolve the thymol iodide in the chloroform and add the ace- 
tone. Prepare as directed for iodoform gauze, dry. 

Chloroform is the best single solvent for thymol iodide, although 
no one solvent dissolves it entirely. Acetone is, however, the 
cheaper and, in the combination above, works satisfactorily. 

Thymol Iodide Gauze, 5 Per Cent., Moist. 



DRY THYMOL IODIDE GAUZE, ICQ GM. 

Water 75 c.c. 

Glycerin 5 Gm. 

Prepare as directed for iodoform gauze, moist. 

Sublimated or Bichloride Gauze (Dry), i-iooo. 

Mercuric chloride .1 Gm. 

Water 37.5 c.c. 

Acetone 37.5 c.c. 

Sterile gauze 100. Gm. 



Dissolve the mercuric chloride in tlie acetone and water and 
proceed as under iodoform gauze, dry, but resterilize for one half- 
hour. 

Sublimated or Bichloride Gauze (Moist), i-iooo. 



Mercuric chloride .1 Gm. 

Water 75. c.c. 

Glycerin 5 Gm. 

Sterile gauze 100. Gm. 



Dissolve the mercuric chloride in the water and add the glycerine. 
Proceed as directed for iodoform gauze, dry, but pack in sterilized 
amber glass jars. Have jar lids loosely placed, then put jars into 
steam bath and resterilize for one half-hour. Hermetically seal 
immediately upon removal from the sterilizer. 

Phenolated or Carbolized Gauze, 5 Per Cent., Dry. 



Phenol, crystals 5 Gm. 

Acetone 50 c.c. 

Water 50 c.c. 

Sterile gauze 100 Gm. 



Mix the acetone and the water, add the phenol, and proceed 
as for iodoform gauze, dry. Resterilization is used for only fifteen 



Am. Jour. Pharm. ) 
April, 1911. ; 



Medicated Gauges. 



183 



minutes in this case because of the ease with which the phenol may 
be volatilized through the wrapping. While a small amount of 
moisture remains in the product when finished, it will dry rapidly 
after packing. 

Phenolated or Carbolized Gauze, 5 Per Cent., Moist. 



Phenol, crystals 5 Gm. 

Acetone 50 cc. 

Water 50 cc. 

Glycerin 5 Gm. 

Sterile gauze 100 Gm. 



Mix the acetone, water and glycerin and dissolve the phenol in 
the mixture. Proceed as for iodoform gauze, dry, but pack, upon 
removal from impregnating jar, into sterilized amber glass jars and 
resterilize in a steam bath for one half-hour, having the lids of the 
jars loosely placed. Hermetically seal immediately upon removal 
from the sterihzer. 



Borated Gauze, 10 Per Cent., Dry. 

Boric acid 10 Gm. 

Water 100 cc. 

Sterile gauze 100 Gm. 

Dissolve the boric acid in the water by heat and proceed as for 
iodoform gauze, dry, excepting that the material should be kept 
at the temperature of boiling water till the moisture is evenly dis- 
tributed, and then pack without further drying. Resterilize for 
one half-hour. 



Borated Gauze, 10 Per Cent., Moist. 

Boric acid 10 Gm. 

Glycerin 5 Gm. 

Water 100 cc 

Sterile gauze 100 Gm. 

Dissolve the boric acid in the glycerin and water with the 
aid of heat. Proceed as for above, but pack in jars and finish as 
under iodoform gauze, moist, excepting that resterilization should 
be continued for one half-hour. 



i84 



Medicated Gauges. 



/Am. Jour. Pharni. 



1 April, 1911. 



Picric Acid Gauze, 2 Per Cent., Dry. 



Picric acid . 

Water 

Acetone .... 
Sterile gauze 



2 Gm. 
.50 c.c. 
50 c.c. 

TOO Gill. 



Dissolve the picric acid in the acetone and water and proceed 
as under iodoform gauze, dry. 



Dissolve the picric acid in the glycerin, water and acetone and 
proceed as for phenolated gauze, moist. ■ 

All gauzes for medication should be sterilized just before being 
used. This should be preferably, by dry heat at a temperature of 
I20°-I50° C. for one half-hour, as many of the moistening liquids 
cannot be satisfactorily applied to any but dry material. 

The amount of solution required for the impregnation of a given 
amount of gauze will vary slightly according to the number of 
threads to a given unit and the tightness of twist of the fabric. 

Glycerin and acetone are not miscible, except upon the addition 
of water. Hence, it will be noted that gauzes prepared with ma- 
terial insoluble in water are moistened, where required, with 
glycerin solutions after impregnation. ' 

In working out these formulas the question as to method of 
figuring the percentages arose. It will be noted that the percentage 
of medicament is based in each case upon the amount added to 100 
parts of dry gauze. It is obvious that this furnishes the most 
convenient and most satisfactory means of figuring. The generally 
adopted method of parts in 100 parts of finished product, would 
be uncertain because of the variability of the moisture content 
through sterilization. Then, too, the weight of gauze taken is 
never exactly that given in a formula, but, in the nature of the case 
must be either a fraction or a multiple of the same and, often, an 
exceedingly inconvenient figure for calculation. For instance, work- 



PicRic Acid Gauze, 2 Per Cent., ^Ioist. 



Picric acid . 
Glycerin . . . , 

Water 

Acetone .... 
Sterile gauze 



2 Gm. 

5 Gm. 
50 c.c. 
50 c.c. 
100 Gm. 



Am. Jour. Pharm. ) 
April, 1911. / 



Medicated Gauzes. 



ing with 273 Gm. of gauze and a formula based upon 10 parts in 
100 of finished product, 30.33 parts of medicament would be re- 
quired. With the proposed method of 27.3 parts would be required, 
an amount easily and evenly calculated and. weighed. Furthermore, 
if analytical methods are to be applied, it is much easier to remove 
the added material and figure upon a "fixed remainder than upon 
an uncertain total weight. In the German " Erganzungsbuch " a 
formula is given which calls for no parts of iodoform to 1000 
parts of gauze. There has, apparently, been an attempt to har- 
monize the two methods by the addition of an extra 10 parts in the 
amount of iodoform directed, apparently, in order to make the 
finished product exactly 10 per cent. This is, of course, not the 
result. We often see the kitten chasing his tail. But scientific 
authority rarely gives us the opportunity of witnessing a similar 
endeavor upon its part. 

A few formulas for gauzes were given in a previous edition of 
the National Formulary, but were omitted in the last revision, prob- 
ably because, as there directed, they could not be satisfactorily pre- 
pared by the pharmacist. Then, too, they were not of the character 
demanded by modern practice. The writer believes that some of 
the submitted formulas might be admitted into that work with 
advantage. It has been argued again and again that official recog- 
nition would be a mistake, because the pharmacist lacks the facili- 
ties, and it has been hinted that he has not the intelligence and 
training necessary for the careful preparation of surgical dressings. 
These arguments, to say the least, are not very complimentary to 
the ingenuity and ability of the American pharmacist, especially in 
view of the fact that his brethren in Germany, Austria, Switzer- 
land, Belgium, the Netherlands and Italy, prepare such products 
from formulas in their respective pharmacopoeias. 



i86 Quantitative Methods. {^'^'Ai!'^\\'ilu.'°'' 

ABSTRACT OF 
REPORT OF THE COMMITTEE ON QUANTEfATIVE 

METHODS 

Division of Pharmaceutical Chemistry 

OF 

American Chemical Society. 

Your Committee begs to offer the following report of work 
which has been done since the last meeting (July, 1910). In the 
search for suitable assays for the various mercury salts included in 
the U.S. P., for which standards of purity are laid down and no 
assay processes are given, investigation was made of a number of 
existing methods as indicated below. 

In order that you may know the method of working of the 
Committee, we give an outline of the plan pursued in this case. 
The Chairman sent out requests to the members of the Committee 
for suggestions as to methods suitable for general application 
to mercurous and mercuric salts. After going over the suggestions 
received, the following methods as proposed were again submitted 
to the Committee, together with samples of Mercurous Chloride 
and Mercuric Iodide. The methods as submitted are as follows : 

Method No. i. 
Suggested by Mr. L. A. Brown. 
(See Schimpf — Volumetric Analysis, page 408.) 

Applicable to mercurous iodide, chloride, bromide, and mixtures 
of mercuric and mercurous salts. 

Weigh out sample of about 0.5 gramme, place in Erlenmeyer 
flask of about 300 c.c. capacity, add 10 c.c. potassium iodide solution 
containing 2 grammes KI ; rotate and quickly add 50 c.c. N/io 
iodine solution by means of a pipette, agitate until all of the sample 
is in solution. Then run in N/io NaoSoO... solution until all the 
free iodine has been removed, using starch solution if desired. 

Reaction— 2HgCl + 6KI + L = 2KoFgI, + 2KCI. 

By mixing the HgCl with the solution of the potassium iodide 
immediately before adding the iodine solution, the insoluble salt 
goes into solution more quickly. 



"^""'AS'ian*'"" } Quantitative Methods. 187 

Method No. 2. 

Suggested by Mr. L. A. Brown. 

(Merck's Report, 1908, page 57.) 

Applicable to mercuric chloride, iodide, cyanide, nitrate, oxide, 
ammoniated mercury, metallic mercury, and preparations of mercury 
such as ointments of mercury, ammoniated mercury, nitrate, and 
oxide ; solution of mercuric nitrate, Donovan's solution, plaster of 
mercury, etc. 

Dissolve one gramme of the sample {e.g., HgCls) using one or 
two grammes of potassium iodide if necessary, in sufficient water 
to make 100 c.c. of solution. 

Take 20 c.c. aliquot, add i gramme KI, 5 to 10 c.c. of 10 
per cent. KOH sol., and 10 c.c. of water containing 2 or 3 c.c. 
of formaldehyde solution. Mix thoroughly and place on water-bath 
for about 10 minutes, or until supernatant liquid settles clear ; then 
decant off through a small filter, washing residue with two portions 
or more of water, decanting through filter as before. 

Dissolve the small amount of metallic mercury off the filter by 
means of a few drops of hot diluted nitric acid ( i : i ) , washing 
the filter with a few c.c. of water to remove all traces of mercury. 
Collect filtrate and washings in the beaker containing the Hg, 
adding more nitric acid if necessary to secure solution of the mer- 
cury. Evaporate to about 2 or 3 c.c. on a water-bath, then dilute 
with water and transfer to a 100 c.c. flask, rinsing out beaker 
with successive amounts of water sufficient to make 100 c.c. of 
the solution. 

Take an aliquot representing about o.i gramme of HgCls, add 
25 c.c. of water, then a slight excess of 5 per cent, iodic acid solution, 
5 c.c. being enough. This is added drop by drop, agitating all 
the while to secure complete agglutination of the curdy precipitate. 
As soon as the supernatant Hquid is clear, filter and wash precipitate 
with three or four portions of water. 

Dissolve precipitate off the filter with a few drops of diluted 
HQ, wash filter thoroughly, add i or 2 grammes of KI, allow to 
stand for about 5 minutes, then titrate the liberated iodine with 
N/to Na,S,0,. 

Each c.c. of N/to Thiosulphate = 0.0022405 gramme HgCU. 
In the case of ointments, such as official ointments of mercury 



Quantitative Methods. 



A in. Jour. Pharm. 

April, 191 1. 



and its salts, remove the ointment base by means of the proper 
solvent, dissolve the residue with nitric acid, and apply the method 
as given. 

Method No. 3. 
Suggested by Mr. B. L. Murray. 
(See Smith — Electro-Analysis, pages 90 and 94.) 

Applicable to solutions of mercury nitrate, the mercury oxides, 
metallic mercury, mercury with chalk, and possibly some of the 
other mercurial preparations. 

Not applicable to calomel or corrosive sublimate. 

Those preparations of mercury as found in the U.S. P., which 
can readily be brought into solution in nitric acid, are satisfactorily 
assayed for mercury by electrolysis. 

The sample may well be of such a size that the final weighing 
of the metallic mercury will show a weight of about 0.250 gramme. 
The mercury solutions, or the dry preparations dissolved, are 
acidulated with 3 c.c. of concentrated nitric acid, diluted to 125 
c.c, heated to 70° C, and then electrolyzed with a current of 
N.D. 100=0. 06 ampere and two volts. The metal will be fully 
precipitated in from 2 to 4 hours, and may appear as a uniform 
metallic coating upon the platinum dish, which is used as a cathode, 
or it may appear in shiny droplets. After the deposition of the 
material is complete, the mercury is washed with water, then with 
alcohol, then with ether, and finally dried a short time in the 
dessicator and weighed. The electrolyte remaining may be tested 
qualitatively for mercury to show that the deposition was complete. 

The time may be materially shortened by the use of the 
rotating anode and mercury cathode. 

Method No. 4. 

Suggested by Mr. F. O. Taylor. 

(See E. Rupp, Berichte, 1906, 39, 3702.) 

(See also Chem. Zeit., 1910, 34, 229.) 

A solution of the mercury salt, containing about 0.2 gramme 
of mercury in 25 to 50 c.c. of solution, is treated with excess of 
KI so that the Hgia formed redissolves. Render alkaline with 
NaOH ; treat with 3 c.c. of 40 per cent, formaldehyde solution 



^'°ApriU9n*'"' } Quantitative Methods. 189 

diluted with 10 c.c. of water and let stand with occasional stirring 
for about two minutes. Acidify with acetic acid ; add 25 c.c. of 
N/io iodine and after all the precipitated mercury has combined 
with the iodine, titrate the excess with N/io sodium thiosulphate 
solution. 

Mercurous salts must be converted into mercuric before precipi- 
tation. 

In the case of mercuric cyanide, sulphuric acid should be used 
instead of acetic in order to decompose any cyanogen iodide which 
may have formed. 



Method No. 5. 

Suggested by Mr. F. O. Taylor. 

(See C. J. Pretzfeld — J. A. C. S., 1903, page 198.) 

Estimation of Mercury as Arsenate. 

The mercury must be present as a mercuric salt, and preferably 
as a nitrate, as mercuric arsenate is not precipitated from the 
chloride solution. A small amount of free nitric acid does not 
interfere with the accuracy of the results. To a cold solution 
containing about 0.25 gramme Hg in 100 c.c, add 20 c.c. of 
saturated solution sodium arsenate. The heavy yellowish-white 
precipitate of mercuric arsenate immediately forms and settles 
rapidly, but for greater accuracy the author of the method recom- 
mends that the solution stand for several hours ; then filter through a 
Gooch filter, wash thoroughly with cold water and dry at 100°. 



Method No. 6. 

Suggested by Mr. F. O. Taylor. 

(See same paper as above.) 

Estimation of Mercury as Chloride. 

To a solution of tlie mercuric salt, preferably in the form of 
a nitrate containing about 0.25 to 0.4 gramme Hg, add a slight 
excess of a mixture containing one drop of hypophosphorus acid 
to each c.c. of H„0., and then immediately an excess of solution 
sodium chloride. Let stand for one hour, filter off the precipitated 
HgCl, wash thoroughly, dry at 100° and weigh. 



Quantitative Methods. 



Am. Jour. Pharm 
April, 1911. 



Below, in tabular form are given the results obtained by different 
members of the Committee in using these methods. 









Analysis 


OF Mercurous 


Chloride. 










Method No. i. 


Method No. 








Chemist 


Per cent. 


Per cent. 


Mr. 


T 

L,. 


A 

A. 
















99.91 




Mr. 


B. 


L. 




98.94' 












99-33 












99-25 












99-35 












99-23 












99.19 




Mr. 


L. 


D. 




100.46 ^ 


99.84 










99.71 


100.04 










100.01 


99.62 










100.04 


99.84 










100.18 





Special Method* 
Per cent. 



99.62 ' 

99-79 



Mr. F. O. Taylor. 



Comments, 



' Method is entirely satisfactory if closely adhered to. 
^ Method worked well, although some time was consumed in effecting 
solution in iodine. 

^ The factors seemed too large to permit of sufficient accuracy when 
working upon samples of close to 100 per cent, purity. 

* (Mr. Taylor's results are unfortunately unavailable, but his comments 
are at hand.) The chief difficulty with this method is the dissolving of 
the mercury by the iodine solution, which is very often extremely slow. 
Aside from this, the method seems very good. 

^ Samples were dissolved in sodium sulphide solution and electrolized 
three quarters of an hour with 0.5 ampere, 4-5 volts., using mercury cathode 
and rotating anode, (See Jour, Ind, and Eng. Chem., vol. 2. page 481.) 
Results very satisfactory. 



Analysis of Mercuric Iodide. 



Chemist. 
Mr. L. A. Brown. 



Mr. B. L. Murray. 



Method 


Method 


Method 


No. 2. 


No, 3. 


No 4- 


Per cent. 


Per cent. 


Per cent. 


95-74" 




99-67" 






100.39 


79-17" 


98.68 


98.57" 


86.36 


99-38 


99.38 


81.50 


98-52 




86.04 






62.01 






80,82 







Method 
No. 5. 
Per cent, 



Method 
No. 6. 
Per cent. 



Am. Jour. Pharm. ) 
April, 1911. ; 



Quantitative Methods. 



191 



Method 

Chemist. No. 2. 

Per cent. 

Mr. L. D. Havenhill 944o" 

94.19 

94-65 
91.88 

97.65 ' 
98.80' 

97.65 ' 
91.88' 

93.95 ' 



Mr. F. O. Taylor 



16 



Method 


Method 


No. 3, 


No. 4. 


Per cent. 


Per cent. 


97.83 ' 


64.1 " 


97.94 " 


98.64 " 


99.89 " 


97.64 " 


98.86 


98.80 




98.86 




99.58'' 




99.98 " 




99.80 




99.70 




99.62 




100.50 




21 


10 


22 



Method Method 

No. 5. No. 6. 

Per cent. Per cent. 

97.85" 97.98 

93.10 97.84 

98.09 97.60 

94.00 97.51 



Comments. 

' Precipitating and washing in dilute alcohol. 

^ Same solution as preceding® but washing with water. 

' Dried at 50° C. 

® Our work seems to indicate that there was a considerable loss of 
mercury, due to volatilization when the cathode was dried at a temperature 
of 50°. 

Unquestionably the electrolytic method is extremely accurate when 
used by one who is experienced and has at hand the proper apparatus, and 
it can also be made a very rapid method. It does not seem, however, 
to be suited to the requirements of pharmacopceial estimation, as at the 
present time one is much more likely to find the requisite skill and apparatus 
for making other forms of assay than the electrolytic, among those to whom 
these assays would be chiefly valuable. 

"Dried in dessicator at room temperature. 

Mr. L. A. Brown : I got very poor results due possibly to two causes : 
(i) Mechanical loss of mercury in filtering after reduction. (2) Part of 
the mercury appears to come down in a colloidal condition and is lost in 
the filtrate. I have proven to my entire satisfaction that the reduction by 
formaldehyde in alkaline solution is quantitative, and what makes me 
believe that part of the mercury is in a colloidal form is that a perfectly 
clear filtrate will shown the presence of mercury by hydrogen sulphide if 
completely saturated. 

The method gave us uncertain results. 
" Mr. L. D. Havenhill : The amount of water used in washing the 
precipitate of mercury iodate tends to vary the results. 

Thirty seconds with stirring for reduction. 
^'Mr. F. O. Taylor: We find this method inaccurate because of the 
distinct solubility of the mercuric iodate in water, which solubility may 
be proved by testing the filtrate from the mercuric iodate by hydrogen 
sulphide, when a very decided test for mercury can be obtained. 



192 



Q 1 ( an titative Methods. 



( Am. Jour. Pharni 
X April, 1911. 



^' Two minutes with stirring fcr reduction. 
^'^ Four minutes with stirring for reduction. 
^^Five minutes with vigorous shaking. 

'° Mr. B. L. Murray: In using this method we found that two minutes 
was not sufficient time for the reduction of the mercury by formaldehyde. 
Even five minutes was too short a time and a Httle heat was used to 
complete the reduction ; but this we found reduced the mercury to such 
a condition that it was very hard to dissolve in the iodine solution. 

We found the time for reduction to be insufficient, also the stirring. 
Better, or at least higher results were obtained by vigorously shaking the 
mixture. The quantity of acetic acid used is indefinite. Our results, which 
are not herein reported, seem to show that the more acetic acid used, the 
lower are the results. We believe that the size of the factor is too large 
to permit of sufficient accuracy when working on samples that run close to 
TOO per cent, in purity. 

" Here again the difficulty of dissolving the precipitated mercury in 
iodine solution is the chief drawback. With care the method can be made 
accurate, but it usually requires more time than a process of this kind 
should. 

In this method the mercuric iodide was reduced with formaldehyde 
in the manner indicated by the method of E. Rupp, dissolved in nitric acid 
and precipitated with sodium arsenate. It was noted that the precipitate 
of mercuric arsenate was not of uniform color. The higher results here 
reported were obtained from precipitates that were materially whiter in 
color than those (more yellow) precipitates yielding the lower results which 
were more yellow in color. 

Inaccurate results here may be attributed to the slight solubility of 
mercuric arsenate in water, which seems to be sufficient to render the 
method not very desirable. 

No careful work was done by me on this method, but only some 
preliminary tests, and it would appear that special care must be taken in 
the reduction of the mercuric salts and it is therefore preferable to use 
phosphorus acid instead of hypophosphorus acid. 

Contrary to previous observations I find this method to give good 
results if the reduction is carried out in the cold and not allowed to 
stand too long before adding iodine solution. If the reduced mercury is 
allowed to coalesce and form large globules the solution of the mercury 
in the iodine solution is very slow. 



i 



^'^■Ap??r'i9ii*™' } Correspondence. 193 

CORRESPONDENCE. 

American Pharmaceutical Association. 

American Journal of Pharmacy, 
Gentlemen : 

Chairman Beal of the Council of the American Pharma- 
ceutical Association has sent out the following communication: 

J. W. England, 
Secretary of the Council. 

"To THE Members of the Council: 

As a means Of carrying into effect Resolution No. 31, relating 
to the raising of a fund for the liquidation of the indebtedness 
upon the home of the late Professor C. S. N. Hallberg, I have 
appointed the local committees named below, and suggested that 
they work in accordance with the following plan : 

(1) That the several local committees be authorized to join 
with them such additional persons as they may select to assist in 
the soliciting of subscriptions. 

(2) That subscriptions be solicited not only . from members of 
the American Pharmaceutical Association, but from any others 
who may be interested in paying a tribute to the memory of 
Professor Hallberg on account of his distinguished services to 
American Pharmacy. 

(3) That the names of all subscribers to the said fund, with 
the amounts subscribed, be published in the Bulletin of the Asso- 
ciation. 

(4) That the subscription be taken upon the form submitted 
herewith, and that all such subscriptions, when signed, and all 
cash contributions received by the solicitors, be forwarded to the 
Treasurer of the Association, Dr. H. M. Whelpley, 2342 Albion 
Place, St. Louis, Mo. 

I am informed that the title to the Hallberg home is in the 
name of Mrs. Hallberg, and that there remains due upon the same 
approximately the sum of $3,500.00 payable in annual instalments 
of $500.00 each, with interest. 

The Chairman will be grateful for additional suggestions, either 
as to the regulations concerning the taking of subscriptions or 
of names to be added to the several local committees, or to act in 
districts not represented in the list herewith submitted. 

Respectfully submitted, 

J. H. Real." 



194 



Correspondence. 



I Am. Jour. Pliarm 
1 April, 1911. 



AMERICAN CHEMICAL SOCIETY. 

Division of Pharmaceutical Ciieaustrv. 

The Division of Pharmaceutical Chemistry of the Am- 
erican Chemical Society held its Minneapolis meeting in 
the Chemistry Building of the University of Minnesota on 
December 29. The address of Prof. A. B. Stevens (Chairman) 
upon Pharmacopoeial Standardization was especially interesting and 
timely, since Prof. Stevens is a member of the Committee of 
Revision of the Pharmacopoeia, and Chairman of the Sub-Com- 
mittee on Proximate Assays. The address outlined the work being 
done by the Sub-Committee mentioned and made clear the thor- 
oughness and carefulness with which the Pharmacopoeia is being- 
revised. The new and improved methods of committee work were 
also explained. 

The Report of the Committee on Quantitative Methods gave 
a resume of the analysis of Mercury Salts by six different methods. 
The Committee has done valuable work and is being continued. 
The Report, although merely a report of progress, was ordered 
published in order that the greatest benefit may be obtained from 
the work of the Committee. 

The papers read at the meeting were as follows : A. B. Stevens, 
Citro-Compounds of Iron ; E. R. Miller and G. H. Marsh, Camphor 
in Oil of Sassafras; L. E. Sayre, Assay of Gelsemium; F. Klein, 
Rapid Determination of Sulphuric Acid with the Porous Clay 
Crucible ; E. Kremers, Chemical Problems Suggested by the Cul- 
tivation of Medicinal Plants, (i) Stramonium. 

The following officers were elected for the ensuing year : Chair- 
man, B. L. Murray ; Vice-Chairman, A. D. Thorburn ; Secretary, 
F. R. Eldred. Members of Executive Committee : A. B. Stevens, 
L. F. Kebler. 

B. L. Murray. 

Chairman. 



I 



From the painting by Mr. Hugh H. Breckenridj^e. 



MR. HOWARD B. FREx\CH, Ph.G. 
President Philadelphia College of Pharmacy. 



THE AMEEICAH" 

JOURNAL OF PHARMACY 



MAY, igii 



THE IDENTHHCATION OF COCAINE AND SOME 
COCAINE SUBSTITUTES. 

By Francis J. Seiter and Frederic Enger. 

During the last five years, a large number of specimens, con- 
taining cocaine, has been examined in this laboratory. This work 
was done for the Chicago police department, which has been striving 
to stamp out the illegal sale of cocaine to habitual users of the 
alkaloid. 

The chief difficulty which presented itself in the analysis of 
the specimens was the small amount of material submitted by the 
police officers. The weight of an average specimen was ap- 
proximately O.I gram. The specimens frequently contained acetan- 
ilide in amounts varying from 20 per cent, to 80 per cent. Some 
of the catarrh powders, e.g., Dr. Gray's Catarrh Powder, contained 
but 8 grains of cocaine hydrochloride to the ounce. As in all these 
cases a portion of the specimen was reserved for exhibition in 
court, the quantity of alkaloid available for identification was so 
small as to render imperative the adoption of a scheme of analysis 
whereby the material might be economized without sacrifice of 
accuracy. 

Many of the proposed tests for cocaine require considerable 
quantities of the alkaloid and yield results not characteristic of 
cocaine alone. Among these may be mentioned the tests with 
concentrated mineral acids, with or without the addition of oxidizers 
or other substances used in color reactions and the test involving 
the detection of the benzoyl group, which requires at least 0.2 gram, 

(195) 



196 • Identification of Cocaine. {^'^'£y\^i'''^' 

according to Autenrieth.^ This test is not reliable, however, as 
it is also given by alpha- and beta-eucaine, stovaine and, in fact, 
by any of the cocaine substitutes containing the benzoyl group. 

The tests which fulfilled our requirements most satisfactorily, 
and which we adopted in our work, are based upon the following 
observations. Cocaine salts will react, under certain conditions, 
with gold chloride, platinum chloride, chromic acid and potassium 

Fig. I. 




Cocaine chloro-platinate, x 100. 



permanganate to form precipitates which, when examined under 
the microscope, are found to possess definite and characteristic 
crystalline forms. 

The test solutions required are — i per cent, solutions of gold 
chloride, platinum chloride and potassium permanganate and a 5 
per cent, solution of chromic acid. 

The alkaloid, isolated in the usual ways, is converted into the 
hydrochloride and made up to a 2 per cent, solution. A small por- 



^ Autenrieth, Auffindung der Gifte, 3 Aufl., page 79. 



Am. Jour. Pharm. | 
May, 1911. / 



Identification of Cocaine, 



197 



tion of this 2 per cent, solution, say ^ c.c, is set aside for the 
permanganate test. The remaining solution is diluted with an 
equal volume of water, forming a i per cent, solution. Portions 
of y2 c.c. of this solution are reserved for the platinum chloride 
and chromic acid tests. To a third ^ c.c. portion of the i per 
cent, solution is added i c.c. water and the resulting liquid used 
for the gold chloride test. 

Fig. 2. 




Cocaine-chloro-aurate, x loo. 



POTASSIUM PERMANGANATE TEST.'' 

To ^2 C.C. of a 2 per cent, solution of cocaine are added five 
drops of permanganate test solution. A precipitate is formed con- 
sisting of violet-red, rectangular plates. The other common alka- 
loids either immediately or slowly reduce the permanganate without 
forming crystalline precipitates.^ This is also true of the cocaine 
substitutes, holocaine, acoine, and euphthalmine, which almost in- 



^ F. Giesel, Pharm. Zeit., 1886, p. 132. 

'Allen, Comm. Org. Anal. 2d Ed., vol. iii, pt. ii, p. 144. 



198 



Identification of Cocaine, 



JAm. Jour. Pharm. 
1 May, 1911. 



stantly reduce the permanganate. Alpha- and beta-eucaine and 
stovaine do not reduce the permanganate immediately, resembling 
cocaine in this respect. No crystals, however, are formed in these 
cases. 

The permanganate reaction requires a fairly concentrated solu- 
tion of cocaine, but there is no difficulty in obtaining the charactcr- 



FlG. 3. 




Cocaine permanganate, x 100. 



istic violet-red plates in a 2 per cent, solution. " With a one 
per cent, solution, the crystals (of cocaine permanganate) only 
form as evaporation takes place." * 

PLATINUM CHLORIDE TEST.^ 

To y2 c.c. of a one per cent, solution of cocaine are added 
two drops of platinum chloride test solution. The test tube should 
not be shaken, as larger and better formed crystals will result 



* Allen, Comm. Org. Anal. 2d Ed., vol. 11 1, pt. ii, p. 276. 
"A. B. Lyons, Am. Jour. Pharmacy, Ivii, No. 10. 



Am. Jour. Pharm. 1 
May, 1911. J 



Identification of Cocaine. 



199 



when the solution is undisturbed. A buff colored precipitate is 
formed which, under the microscope, appears as large feathers or 
plumes, sometimes arranged in stellate pattern. In higher dilutions 
(1:600) crystals slowly form which ''resemble carpet tacks." ^ 

Alpha-eucaine, with the above test, gives bundles of fine needles ; 
beta-eucaine, after 30 minutes^ gives a few very large, broad leaves, 
rosettes and cubes ; holocaine gives small stars ; acoine gives an 
amorphous precipitate, while stovaine and euphthalmine give no 
precipitates. None of the precipitates yielded, by the cocaine sub- 
stitutes resemble the cocaine chloroplatinate in any way. 

GOLD CHLORIDE TEST."^ 

To one c.c. of a dilute solution ( i : 300) of cocaine are added 
three drops of gold chloride test solution, avoiding shaking as in 
the case of the platinum chloride test. A precipitate immediately 
forms and slowly changes from the amorphous into the crystalline 
state. Under the microscope, the crystals resemble fern-fronds, 
generally with a stellate arrangement. In dilutions of i : 12,000, 
similar crystals form, after long standing. 

With the gold test, alpha-eucaine gives branching, twig-like 
crystals ; stovaine gives large crystals resembling those of cocaine 
chloroplatinate in general structure, but differ in that the branches 
possess smaller branches, which is not the case with the cocaine 
chloroplatinate. Amorphous precipitates are given with beta- 
eucaine, acoine and holocaine. Euphthalmine gives no precipitate. 

CHROMIC ACID TEST.* 

To y2 c.c. of a one per cent, solution of cocaine are added two 
drops of chromic acid test solution and then concentrated hydro- 
chloric acid, drop by drop with shaking, until the precipitate 
dissolves. After a short time, clusters of fine needles separate out 
and the solution remains yellow for several days. 

Alpha-eucaine gives a precipitate which requires a large volume 
of hydrochloric acid for complete solution. The liquid remains 
yellow for several days but no crystals form. Beta-eucaine and 
stovaine behave like cocaine but no crystals separate out in either 



"Allen, loc. cit., p. 275. 
^ A. B. Lyons, loc. cit. 

" K. Metzger, Pharm. Zeit., xxxiv, 697, also Allen, loc. cit., p. 276. 



200 



Identification of Cocaine. 



Am. Jour. Pharm. 
May, 1911. 



Ph 

ft 
O 



ft 
ft 

o 



ft 
ft 
O 



Pi 
o 



o 
ft 

o ^ 

a 



:3 

o 

ft 

^ +^ 
o a 

a ^ 

< 



"rt ^ 

^ 

^ a ^ 



ft-^ 
m r< O 

o o 



ft 

u ^ O 

oj n3 c/3 



O 
ft 

O ft 

a ^ 
< 



13 13 ^ 

^ 5^ <1J 

^ S t-i • 

^ a ^ I 



C/3 O 

>^ U 

u 

o o 



O 'O 



'd 



"3 r.' 

u o 



aj )H ^ 



+-> "d 
u 

^ O 

o ^ 



;3 
o 

ft 
o 

a 



o ^ ^ 



o o 
o ^ 



b/3 



03 



O ° ^ 

o c/2 



>^ in 
U 

O O 



:3 



^ . 
.,-1 w 



0) 



03 .2 

O 

w C/2 'd 



'd 'd 

(U CU 

^ o 



Am. Jour. Pharm. \ 
May, 1911. / 



Standardisation of Digitalis. 



201 



case. Holocaine gives a precipitate soluble in hydrochloric acid, 
but no crystals form and the solution turns green on standing. 
Acoine gives a precipitate soluble in hydrochloric acid. After a 
short time, a brown precipitate forms and the supernatant liquid 
becomes brown, slowly changing to green. Euphthalmine gives no 
precipitate with chromic acid test solution. 

Cocaine solutions will yield crystals with chromic acid in 
dilutions of i : looo. 

The behavior of cocaine with the chromic acid test is not 
duplicated by any of the other common alkaloids.® 

In addition to the above tests, the behavior of chlorine water 
with the cocaine substitutes has given valuable results which serve 
to differentiate between these and cocaine. To i c.c. of a one 
per cent, solution of alkaloid are added 2 c.c. of saturated chlorine 
water. Cocaine gives no precipitate; alpha-eucaine, a milky tur- 
bidity ; beta-eucaine, a dense white turbidity ; holocaine, a light 
yellow turbidity ; stovaine, a light milky turbidity ; acoine, a maroon 
precipitate and claret solution, and euphthalmine, no reaction. 

The results of all the foregoing tests are appended in tabular 
form on the opposite page. 

The micrographs, representing a magnification of 100 diameters, 
were kindly made for us by Mr. Carl S. Miner, Ellsworth Building, 
Chicago, for which we wish, in this place, to express our ap- 
preciation. 

PHYSIOLOGICAL METHODS FOR THE STANDARD- 
IZATION OF DIGITALIS. 

By Charles C. Haskell, A.B., M.D., Indianapolis, Ind. 

It seems to be generally admitted that there is no satisfactory 
method for the chemical assay of the drugs of the digitalis series. 
Reed and Vanderkleed claim to have found an agreement between 
the values obtained for digitalis preparations through physiological 
tests and those obtained through determination of the digitoxin con- 
tent, but their experience is practically unique, other investigators 
being able to see no such agreement. Inspection shows, moreover, 
that the results secured even by Reed and Vanderkleed are not at 



•Metzger, loc. cit. 



202 Standardisation of Digitalis. {^"'Maria^i*'" 

all convincing. In view of this fact, much work has been done in 
the attempt to secure a satisfactory method of physiological assay 
for the heart tonics. 

Changes in the blood pressure and heart rate of a mammal 
following the intravenous administration of digitalis are, in all 
probability, proportional to the therapeutic value of the drug. It 
has been shown, however, that this method of testing is not suited 
for accurate standardization of the drugs belonging to the digitalis 
group. The same preparation injected into difierent animals will 
cause different percentage increase in blood-pressure and decrease 
in heart rate; while if a standard be injected with the purpose of 
comparing its action with that of the preparation to be tested, this 
standard will modify the results, secured by the subsequent injection 
of the drug of unknown strength, owing to the fact that the digitalis 
bodies are very slowly destroyed or eliminated by the animal 
organism. 

The perfusion of the isolated mammalian heart also offers a 
satisfactory qualitative test for digitalis, but the technic is difficult 
and Sowton has shown that the method is not suited for quan- 
titative determinations. 

The methods now commonly advocated may be divided into: 

I. Those upon frogs. 

A. Houghton's 12-hour method. 

B. Focke's method. 

C. One-hour method. 

II. Those upon mammals. 

A. Guinea-pig method. 

B. Hatcher's cat method. 

To Houghton belongs the credit of first employing physiolog- 
ical tests for the commercial standardization of the heart tonics. 
The method which he proposed in 1898 and which, with slight 
modifications, is still employed, rests upon the determination of the 
minimum lethal dose of the drug for a frog, usually Rana pipiens. 
A series of frogs is injected, into the anterior lymph sac, with varying 
doses of the preparation to be tested ; and at the same time, another 
series of frogs from the same lot is injected with a standard. At 
the end of 12 hours, the animals are examined. If the variation of 
dosage has been sufficiently great, certain of the animals are alive, 
while certain others are dead. A second series is now injected with 



Am. Jour. Pharm. 
May, 1911. 



Standardisation of Digitalis. 



203 



the smallest dose which proved fatal in the first case, and if the 
majority of these are dead at the end of 12 hours, this dose is 
accepted as the m. 1. d. 

Focke's ^ experiments seem to have been carried out on Rana 
femporaria. The animals are fastened to a board and the heart is 
exposed with avoidance of hemorrhage. The drug, in the form of 
an infusion, is injected into the femoral lymph sacs, and the time 
noted before systolic stoppage of the heart. 

A factor V is then determined from the weight of the frog, 
size of the dose, and lapse of time before systolic stoppage of the 
heart. 

The one-hour frog heart method was originated by Cushny * and 
is now much used by his pupils, Edmunds and Hale. (The method 
proposed by Fraenkel ^ in 1902 differs from this in several important 
details.) It resembles Houghton's method in that the frogs are 
injected in series and comparison is made with another series in- 
jected with a standard preparation. At the expiration of exactly 60 
minutes, however, the animals are pithed and the hearts exposed. 
When just the proper dose or an amount slightly in excess has been 
injected, the heart presents a characteristic picture ; the auricles 
purple and distended; the ventricle white, motionless, and con- 
tracted. 

In 1908, Reed revived the guinea-pig method for determining 
the strength of preparations of the " heart tonics." Laborde and 
Duquesnel,^^ in 1884, were apparently the first to use the guinea-pig 
in such tests, their investigations dealing with two samples of 
" digitalin/' the solutions of the drug being injected subcutaneously 
or intramuscularly. In 1888, Gley ^ compared the toxicity of oubain 
and strophanthin, using guinea-pigs and other animals. When 
Houghton,^^ in 1898, published his method for the assay of 
strophanthus, he stated that he had employed guinea-pigs, as well 
as frogs and other animals, upon which to perform experiments. 

Reed believes that frogs are unsuitable animals tO' employ in 
these tests, because they vary in their resistance to the drug accord- 
ing to season, species, and weight ; while the guinea-pig " does not 
appear to offer so wide a variation." In the same year, Crawford ^ 
pointed out the unreliability of frogs, their powers of resistance 
depending upon season, sex, and room temperature. He considers 
that : " Dr. Reed, of Philadelphia, has made an important advance 
by using guinea-pigs, animals which are more resistant to injury." 



204 Standardization of Digitalis. {'^■"■^^"^9^1*™' 

Githens ^ is firmly convinced of the superiority, as experimental 
animals, of guinea-pigs over frogs. The latter are markedly in- 
fluenced " by external surroundings, temperature, amount of moist- 
ure present in the cage, relation of time of feeding to time of 
injection, etc. The species of frog also makes a difference, and, 
according to many authors, the time of year." The guinea-pig, on 
the contrary, " show^s no such variation." The use of a standard 
preparation for comparison with the preparation to be tested is 
unsafe, because the standard is " dependent on the keeping prop- 
erties of a stock galenical, and these are exceedingly uncertain in 
many drugs." 

Finally, the committee on pharmacological assay, of the Philadel- 
phia branch of the American Pharmaceutical Association,^'^ advocates 
the adoption of the guinea-pig method as the official method of 
assay for digitahs. Frogs, they state, vary according to species, 
season of year, and locality. " Guinea-pigs, on the other hand, are 
obtainable in all parts of the world . . , their susceptibility to 
digitalis, so far as is knozmi, does not vary under ordinary con- 
ditions. Temperature, food, season, weight, and sex do not in- 
fluence their reaction." The members of the committee are con- 
vinced that the use of a standard preparation is unsafe, because this 
standard may vary in strength and cause error in testing the 
preparation of unknown strength. 

Granting that the guinea-pig is a better experimental animal 
than the frog, do the methods present any differences ? In speaking 
of the frog methods. Reed says : " It is, after all, only a toxic 
effect, and the fact that the frog dies with its heart in systole is 
not any more characteristic than the mammalian heart in diastole. 
In either case, the animal dies, and the cause of its death is the 
action of digitalis on the heart." Crawford ^ also considers both 
frog and guinea-pig methods to rest upon the determination of the 
m. 1. d. Githens ^ discusses the matter rather fully. " The 
physiologic action of these drugs, on which their therapeutic value 
depends, is mainly a stimulation of the heart, shown by more 
forcible contraction of its walls. The drugs kill either by inducing a 
state of constant contraction (death in systole) or by overworking 
the heart muscle to such an extent that it gives way to a more or 
less sudden exhaustion with relaxation (death in diastole). In 
either case the effect is primarily due to stimulation of the heart, and 
thus varies in accord Avith the physiologic or therapeutic activity. 



Am. Jour. Pharm. ) 
May, 1911. / 



Standardization of Digitalis. 



205 



. . . occasionally in mamimals the respiration ceases before the heart 
has come to a standstill. This does not indicate any direct action 
of the drug on the respiratory centres, but is due to interference with 
the function of the medulla, dependent on the disturbance of its 
blood-supply. The death is thus due to the stimulating action on 
the heart, however it may eventually occur.'' 

The Philadelphia committee find that the only essential differ- 
ence in the methods is that the question of absorption plays an 
important part if frogs are used. They state that Edmunds and 
Hale shoiwed ''the fatal dose for 12 hours is about three-fourths 
of that for one hour. It is evident that the difference between the 
dose required to kill in one hour and that required to kill in 12 
hours is largely a question of rapidity of absorption. Now, it may 
easily be that a preparation which is highly active may be, for some 
reason, comparatively slowly absorbed, so that the one-hour test 
is not only of activity of the drug, but of absorbability, which is 
manifestly not the purpose of the assay." 

Hatcher believes that the cat is especially suited for the assay 
of these drugs. By the intravenous administration of the prepara- 
tion to be tested, a method simpler, cheaper, more accurate, and 
less time-consuming than those usually employed is secured. 

The simplicity of this method is not very apparent, necessitating, 
as it does, anaesthetizing the cat, dissecting out the vein, and in- 
sertion of a canula. It has not been our experience that cats are 
cheap or easily obtained. According to the tables Hatcher gives, 
with digitalinum verum there was an error of 20 per cent. ; with 
digitalin, of over 55 per cent. ; with impure adonin, of 9 per cent. 
Further, in a note he says : ... we have found a number of cats 
which tolerated doses up to nearly 50 per cent, more than that 
stated." The actual time of one assay is 90 minutes, but when it 
is realized that a certain amount of preliminary preparation is 
needed, it is evident that running two animals^, the minimum number 
from which reliable results could be obtained, will consume over 
three hours. 

That these experienced pharmacologists should, after mature 
consideration, come to such conclusions is a fact that makes me 
hesitate to take a contrary view. It does appear, however, that 
certain points in favor of the frog methods have not been fully 
brought out ; nor have certain important draw-backs to the mam- 
malian method been given the prominence that is proper. Moreover, 



2o6 Standardization of Digitalis. {^"'Ma^im*""* 

some of the statements of Reed and Githens, unsupported by experi- 
mental proof, are rather at variance with the commonly accepted 
views regarding the pharmacology of digitalis. 

To summarize the statements of the authors I have mentioned 
above, we learn that: 

L Frogs vary markedly in resistance to digitalis poisoning.. 

11. That the adoption of a standard is unsafe because of the 
uncertainty regarding the strength of this standard. 

in. That guinea-pigs react with much uniformity to digitalis. 

IV. That absorption plays an important part in the frog 
methods. 

V. That guinea-pig and frog methods are lethal dose methods ; 
death in both cases resulting from the action of the drug on the 
heart. 

As suggested by Houghton, crystalline strophanthin, also 
known as strophanthin gratus or ouabain, is an ideal substance for 
a standard. Possessing, as it does, the characteristic " digitalis 
action on the frog's heart, it is a definite chemical compound, and 
the question of variability of strength or deterioration does not 
come intO' play. By means of this ouabain, each frog lot can be 
standardized, and the possibility of error arising from uncertain 
reaction of the frog eliminated. 

It is indeed commendable with what care some of the authors 
I quoted have scrutinized the frog methods in the effort to discover 
defects from the unfitness oi the animal. The same amount of 
scrutiny has not, apparently been bestowed upon the guinea-pig. 
Reed contents himself with saying that this animal " does not 
appear to offer so wide a variation " ; Githens ^ says that it " shows 
no such variation " ; while the Philadelphia committee modifies 
its claim as to constant resistance in guinea-pigs by adding : So 
far as is known." 

In this connection, it is of interest to mention some of the 
results secured by Arms ^ in animal inoculations. 

Two pigs inoculated with emulsion of nervous tissue from rabid 
dog: one developed typical paralysis on nth day; second showed 
no evidences of injury and was normal at autopsy 13 months later. 
Two pigs inoculated with emulsion from another rabid dog; one 
died same night; other showed no evidences of injury and examina- 
tion of brain was negative six months later. The following day, 
a third pig was inoculated with emulsion from this same dog; no 



^""M^y.^m*'"'"*} Standardisation of Digitalis. 207 

evidences of injury and careful examination of many sections of 
both hippocampus major and cerebellum gave a negative result " 
13 months later. Several instances cited, showing uncertainty in 
reaction of guinea-pigs to glanders infection. " Aside from these 
cases, we have several times failed to get a reaction in the pigs 
when the potato cultures from the swabs showed typical colonies 
and these injected into pigs proved to be B. mallei." 

Doubtless, numerous investigations have been carried out to 
show that guinea-pigs do not vary in their resistance to digitalis 
intoxication, but I have been unable to find the report of a single 
series of experiments performed with the object of showing that 
guinea-pigs are not fully as much influenced by adventitious cir- 
cumstances as are frogs. On the other hand, Houghton states 
that he found guinea-pigs unsatisfactory as compared to frogs and 
Gley ^ mentions variability of the animals depending upon weight, 
and, as most important cause, the " physiologic factor," the degree 
of organic resistance, due to individual peculiarities. In view of 
these statements and the rather suggestive results of Arms, it would 
seem advisable to make such a report before advocating the use 
of guinea-pigs to the exclusion of other animals. 

The Philadelphia committee state that Edmunds and Hale 
found that only three-fourths of the dose necessary to cause systohc 
stoppage of the frog's heart within an hour was needed to kill the 
animal in 12 hours. In the bulletin containing the report of 
Edmunds and Hale,^ the results secured by each of the frog 
methods is summarized. Comparing these results in tabular form, 
we have: 





M.L.D. 


in 12 hours. 


I hour method. 


Preparation 


cc 


mgms. 


cc mgms. 


B. W. & Co. 


0.015 


1-5 


0.020 2.0 


Mulford No. 2 


0.020 


2.0 


0.016 1.6 


S. & D. • 


0.027 


2.7 


0.027 2.7 


P. D. & Co. 


0.029 


2.9 


0.021 2.1 



It is seen that only in one instance was the dose determined by 
the 12-hour method smaller than that determined by the one-hour 
method. I shall endeavor to point out later that these methods 
are not similar and we should not expect the same results. One 
advantage possessed by the one-hour method is that the lymph sac 
is opened preparatory to exposing the heart and any unabsorbed 
drug is discovered, enabling us to disregard that animal, an ad- 



208 



Standardisation of Digitalis. 



( Am. Jour. Phftrm. 
\ May, 1911. 



vantage certainly not possessed by the guinea method, for Nestor 
has shown that with rabbits, digitahs injected subcutaneously often 
becomes encysted and is not absorbed. Focke is convinced, from 
many control experiments, that the question of absorption does not 
influence the results secured by the use of his method, in which 
the end is reached in from 8^ to lo minutes. 

The statements that digitalis always kills mammals by its action 
on the heart is not generally admitted. Edmunds and Hale ^ say : 
" On both mice and guinea-pigs, however, the cause of death in 
probably every case is not due to an action upon the heart, but upon 
the medulla. In every animal we examined we found the heart 
beating after the respiration had stopped and it continued to beat as 
long as artificial respiration was maintained.'' Cushny ^ also states : 
" This stimulation , like that of picrotoxin, seems almost entirely 
limited to the medulla oblongata in many cases. . . . These alterations 
are much greater than those caused by the interruption of the circu- 
lation, and are, therefore, independent of the action on the heart 
to which they have been erroneously ascribed. . . . To^ the same 
cause is to be attributed the rapid, deep respiratory movements and 
convulsions which are often observed in the later stage of poisoning 
and which are evidently not due to cerebral anaemia, as has been 
supposed, for the brain at this stage receives quite as much or more 
blood than it normally does." 

In a very thorough investigation carried out upon rabbits, 
Nestor concludes that death from digitalis poisoning is always 
due to the action of the drug upon the respiration. He shows that 
when the symptoms of intoxication are of the most distressing kind, 
the institution of artificial respiration causes them to disappear. 
He shows that if a rabbit is given a dose of digitalis of such size 
that, uninterfered with, it always causes death, this animal can be 
saved by the maintenance of artificial respiration for several hours. 
He shows that the amount of digitalis which always kills the intact 
animal, when added to the liquid circulating through the perfused 
rabbit's heart, never causes cessation of the cardiac contractions. 
Finally, he removed the hearts of rabbits dead from digitalis poison- 
ing and saw them commence to beat normally when perfused with 
Ringer's solution. " D'une fagon absolument constante les coeurs 
reprenient vie et battaient bien. Ft ce n'est pas seulement le coeur 
du lapin qui pent se comporter de la sorte apre's I'intoxication 
digitalique, mais nous avons repete les experiences avec le coeur du 
cohaye, du rat, et du pigeon." 



Am. Jcmr. Pharm. ) 
May, 1911. / 



Standardisation of Digitalis. 



209 



All lethal dose methods are objectionable, because they offer 
nothing characteristic. The fact that a given preparation is capable 
of killing an animal is certainly no proof of its therapeutic value. 
The active glucosides of digitalis may become decomposed into such 
bodies as digitalresin and toxiresin, which, resembling picrotoxin, 
have a depressant action on the heart, and a preparation containing 
a large amount of such decomposition products, while testing high 
by lethal dose micthods, might not only be below standard, but 
capable of causing dangerous poisoning. On this account, Hough- 
ton's method is open to criticism. Still less satisfactory, however, 
is fthe guinea-pig method, for, in addition to being only a lethal 
dose method, the animal probably always dies from the action of 
the drug on the central nervous system. As Edmunds and Hale ^ 
put it, " One solution might be very weak in its action upon the 
heart and yet contain decomposition products of digitalis whose 
typical action is upon the medulla, and it would, therefore, appear 
unduly strong when judged by such a standard. For this reason, 
we think that methods which employ as a standard the minimum 
lethal dose upon the higher animals are not applicable to the 
physiological assay of digitalis series." 

It is in this respect that the one-hour and Focke's methods are 
much superior. In both of these, the condition of the heart is taken 
as a criterion. That this action on the heart occurs before the 
death of the animal. is shown by the not uncommon observation of 
frogs able to crawl around and very much alive but whose hearts 
present the characteristic " digitalis " picture when the thorax is 
opened ; a picture produced by no drug with which I am acquainted 
except digitalis and its allies. I am convinced that such animals 
as these would recover from the intoxication produced by digitalis 
if they were not molested and the point should be emphasized thai 
these " frog heart " (Focke's and the one-hour method) methods are 
not lethal dose methods. Focke's method is rather complicated and 
the fact that it necessitates opening the thorax of an unpithed frog 
should prevent its adoption. 

That the two " frog heart " methods are accurate within 10 
per cent, is admitted. The cost is a feature that must be considered 
in any commercial method of assay, and a dozen frogs can be 
purchased for the same amount as one guinea-pig ; thereby enabling 
many more control experiments with frogs for the same monetary 
expenditure for material. 



2IO 



Standardization of Digitalis. 



( A.m. Jour. Pharm. 
\ May, 1911. 



The final test of any method of drug assay must rest with the 
cHnician. So far as I can learn, no such clinical trial has been 
made of the guinea-pig method ; while Pratt in this country and 
Focke ^ in Germany, have shown conclusively that the therapeutic 
value of digitalis leaves runs parallel with the potency as determined 
by the frog heart " methods. 

In conclusion, we may say: 

1. That the variations in the reaction of frogs can be nullified 
by the use of ouabain as a standard. 

2. That it has certainly not been proved that guinea-pigs possess 
any marked advantages as experimental animals for testing digitalis 
over frogs. 

3. That lethal dose methods are unsafe, while the one-hour frog 
heart method is both a good qualitative and quantitative test for 
the heart tonics. 

I wish to acknowledge my indebtedness to Dr. J. P. Simonds 
and Mr. C. R. Eckler for assistance in the collection of data. 

Pharmacological Laboratory of Eli Lilly and Company, 
Indianapolis, Ind. 

BIBLIOGRAPHY. 
^ Arms, B. L. : " Some Freak Results from Animal Inoculation." A., 

Journal of Public Hygiene, vol. xix, No. 3. 
^ Crawford, A. C. : " Notes on Physiological Testing," Am. Journal of 

Pharmacy, July, 1908. 
* Cushny : " Pharmacology and Therapeutics, or the Action of Drugs." 

Fifth edition. 

'Edmunds, C. W., and Roth, G. B. : " Physiologic Assay of Nitro- 
glycerine Tablets, Digitalin Tablets, and Fluidextract of Ergot." Jour. 
Am. Med. Assoc., Dec. 19, 1908. 

" Edmunds, C. W., and Hale, W. : " The Physiological Standardization of 
Digitalis." Bl. 48, Hyg. Lab., U. S. Public Health and Marine Hospital 
Service. 

° Fraenkel : " Ueber die physiologische Dosirung von Digitalispraparaten." 
Therapie der Gegenwart, vol. 4, 1902, p. 106. 

' Focke, C. : " Die Physiologische Wertbestummung der Digitalisblatter." 
Arch, der Pharmazie, Bd. 241, 1903 ; " Der Jetizige Stand der Digitalis- 
prufung; Ihr Wert fiir die Praxis und fur die Forschung." Ibid, 
Bd. 247, 1909; "Die Kurzzeitige Injektionsmethode der Physiologischen 
Digitalis und Strophanthusprunfung," Ibid, Bd. 248, 1910. 

' Githens, T. S., and Vanderkleed, C. E. : " Physiologic Standardization 
of Cardiac Stimulants and Depressants, etc." American Journal of 
Pharmacy, Oct., 1910. 



Am. Jour. Pharm. 
May, 1911. 



Granatum, 



211 



" Gley : " Sur la Toxicite comparee de Touabam et de la strophanthine." 
Comp. red. hebd. des Seances de I' Acad, des Sciences. Vol. 107, July- 
Dec, 1888. 

^° Hale, W. : " Factors relating to the Standardization of Digitalis." Merck's 

Report, February, 1910. 
"Hatcher, R. A., and Brody, J. G. : "The Biological Standardization of 

Drugs." Am. Jour, of Pharmacy, August, 1910. 
" Houghton, E. M. : " The Pharmacologic Assay of the Heart Tonics." 

Journal of Am. Med. Assoc., Oct. 22, 1898. 
^^Laborde and Duquesnel : "La Digitaline." Compt. rend. hebd. des 

Seances et Mem. de la Soc. de Biol., vol. i, 8th Series, 1884, p. 93. 
" Nestor, Yerneaux : " Sur le Mecanisme de ITntoxication Digitalique." 

Arch. int. de Pharmacod., vol. 18, 1908. 
Pratt, J. H. : " On the Importance of Determining the Potency of 

Digitalis Preparations." Boston Med. and Surg. Journal, vol. clxiii, 

No. 7^. 

Reed, E. D., and Vanderkleed, C. E. : " The Standardization of Prepara- 
tions of Digitalis by Physiological and Chemical Means." Am. Journal 
OF Pharmacy, March, 1908. 

" Report of Committee of Philadelphia Branch of the American Pharma- 
ceutical Association on Pharmacological Assay. Bulletin of the Am. 
Pharm. Assoc., Jan., 1911. 

" Sowton, S. C. M. : " Some Experiences in the Testing Tincture of 
Digitalis." British Medical Journal, vol. i, 1908. 



GRANATUM (POMEGRANATE).* 

By John Uri Lloyd, Phar.M. 

Punica granatum has been found in cultivation from the earliest 
historical times. It is now found in all warm countries of the 
world, and frequently as an ornamental plant in this country and 
abroad, where it requires protection during the winter season, 
as it will not endure the cold. It is recorded, e.g., that in 1838 
the pomegranate trees in the neighborhood of London were killed 
by the frost. The form generally grown as ornament is the double 
variety, and consequently barren. The fruit of the pomegranate 

* Bulletin No. 18, Pharmacy Series, No. 4, will give a brief history 
of every vegetable drug of the Pharmacopoeia of the United States, 1900 
edition. This, like other Lloyd Library publications, is not in general 
circulation, being designed solely for exchanging for the publications of 
Societies and Academies of Science Extra copies will be printed for those 
who, before May 15, enclose one dollar to " The Lloyd Library," Cincinnati, 
Ohio. 



212 



Granatum. 



Am. Jour. Phann. 
May, 1811. 



has been esteemed a delicacy from the most ancient time, and we 
often see it offered for sale at our fruit stands. In the West Indies, 
where the plant would thrive naturally, it is not extensively cul- 
tivated, and the writer of this botanical history (C. G. Lloyd), 
who has visited all these islands, does not remember to have seen 
it or its fruit here. Like all cultivated plants, it is liable to 
variation, and several of its forms have been considered distinct 
species and named by several authors ; however, they are all now 
considered forms of one species. 

The pomegranate shrub, according to De Candolle, is originally 
a native of Persia and adjacent countries, but has been cultivated 
and naturalized in the Mediterranean countries, at such an early 
date that it has even been considered indigenous to these countries. 

Pomegranate was included among the vegetables that were held 
sacred by the Assyrians and the Egyptians. The latter nation 
made it a custom to place in the graves of the dead fruits of the 
field and garden, among them pomegranates, specimens of which 
are preserved to the present day. The pomegranate had undoubtedly 
an occult significance with the ancient nations. It was frequently 
used as a mystical emblem in adorning the capitals of Assyrian and 
Egyptian columns, and the Bible (ist Book of Kings, vii, i8, 20) 
tells us that in the building of Solomon's Temple the capitals of 
the columns were decorated with a " network of pomegranates." 
Also (Exodus, xxviii, 33, 34), the hem of the high priest's robe 
was adorned with imitations of pomegranates in blue, purple and 
scarlet, alternating with bells of gold. The pomegranate was one 
of the three fruits brought to Moses by the men that he sent to 
spy out the land of promise. Many other passages scattered 
throughout the Bible refer to our plant, and testify to the esteem 
in which the tree and the fruit (then called riinmon) were held 
in ancient times. The fruit and seed of the pomegranates are often 
mentioned in the Arabian Nights." 

Pomegranates were represented on Carthaginian and Phenician 
medals and on the reverse of the coins of the Island of Rhodes. In 
Greek mythology the pomegranate is very conspicuous and sym- 
bolizes fecundity and abundance. The fruit was dedicated to Juno, 
a deity always represented in sculpture as holding a pomegranate. 

The Greek authors, e.g., Theophrastus, describe the pome- 
granate under the names of " roa " and " roa side " ; also Dios- 
corides, who quite explicitly sets forth the medicinal properties of 



Am. Jour. Pharm. I 
May, 1911, / 



Petrox Preparations. 



213 



the different parts of the plant. Among Roman authors who de- 
scribe the pomegranate and its uses are Cato Censorius, PHny, 
Celsus and others. Subsequent writers, for example, the Arabians, 
in the ninth century, also refer to the pomegranate, but seem to 
have mainly reiterated the substance of the writings of their Greek 
and Roman predecessors. The Arabian Nights " speaks of the 
use of the seed cooked as follows : Every day I cook, five dishes 
for dinner, and the like for supper; and yesterday they sought of 
me a sixth dish, yellow rice, and a seventh, a mess of cooked pome- 
granate seed'' (Adventures of Mercury Ali of Cairo, vol. vii, p. 
185..) Of the writers of the Middle Ages, may be mentioned 
Tragus and J. Bauhinus, the latter giving a most detailed compilation 
of that which was known before his time on the subject of the 
pomegranate, including the myths with which it is connected. It 
was not until the present century, however, that the literature 
of the pomegranate was enriched by the study of its chemical 
aspects. 

PETROX PREPARATIONS. 
By George M. Beringer, Ph.M., and George M. Beringer, Jr., P.D. 

Since the introduction of Oleic Acid and the Oleates to medical 
practice by Prof. John Marshall of London in 1872, much has been 
learned concerning the action and use and the proper forms for the 
application of such medications. 

Following his effort, a number of valuable papers were con- 
tributed to the medical and pharmaceutical journals. In the main, 
these dealt with the chemistry and were directed toward improving 
the methods of preparing the oleates of the alkali and metallic 
bases used in medicine so as to obtain more permanent and definite 
chemical compounds of a character suitable for use in ointments 
or in some cases as dusting powders. Yet in these forms, the 
remarkable penetration and absorbability possessed by Oleic Acid 
that makes it so valuable as a carrier for many medications, was 
but very poorly exhibited or utilized. 

True, the so-called oleates of the alkaloids were simultaneously 
developed. These solutions of alkaloids in oleic acid contain a large 
excess of the solvent that is not needed for chemical reasons nor 
is it desirable for therapeutic activity. Very little attempt has 



214 



Petrox Preparations. 



Am. Jour. Pharm. 
May, 1911. 



been made to make this class satisfactory and pleasant and the dis- 
agreeable rancidity of the oleic acid in such excess has no doubt 
deterred physicians from prescribing them, and statistics, as well as 
our personal experience, show that despite official recognition of a 
number of these oleates, their use is exceedingly rare. 

Subsequent investigations proved that it was not necessary to 
use oleic acid in full strength as a vehicle for medication. Also 
that absorbability of oleic acid is really increased when it is more 
or less saponified by ammonia. Further that such an ammoniacal 
soap was miscible with fixed oils, notably paraffin oil, to produce 
a basic preparation which possessed most valuable properties and 
as a medium promised most extensive application. 

It forms with water an emulsion, and when in practice it is 
rubbed into the surface it penetrates the pores of the skin and 
emulsionizes with the moisture and secretion present in the tissues 
and thus becomes even more rapidly absorbed and distributed than 
is pure oleic acid. 

This basic preparation, which we call petrox, is an excellent 
solvent for many of the substances applicable externally as remedial 
agents in inflammations, congestions, rheumatic or other pains, skin 
affections, etc. Its solvent and penetrating properties certainly make 
it a most valuable vehicle and medium for topical medications. 

Certain of the medicated forms, such as the iodine, methyl 
salicylate, guaiacol and creosote petrox preparations have also been 
recommended for internal administration in gelatin capsules or in 
suspension in milk or wine or other diluent. 

While the names of eminent specialists have been associated with 
the introduction and endorsement of many of the medicated forms 
of petrox, their extensive use is no doubt largely due to the com- 
mercial exploitations of certain pharmaceutical manufacturers. 
These manufacturers have commonly adopted proprietary titles for 
their products and it is to be regretted that some should attempt to 
becloud the real composition and formula by the introduction of 
such vagaries and misleading statements in their literature as " an 
oxygenated hydrocarbon," " partly oxydized hydrocarbon " and that 
the " solid form," recommended as an ointment base, is an " in- 
spissated form of the liquid." 

The British Pharmaceutical Codex and the Erganzungsbuch zum 
Deutschen Arzneibuch each contain a series of formulas for this 
class of preparations. The latter uses as a title " Vasolimentum/' 



"^"^Mayrim*""""} Petrox Preparations. 215 

and the Codex " Parogeiium," and as English synonyms Parogen, 
VasoHment and " Oxygenated Paraffin," thus perpetuating one of 
the vagaries of the proprietary medicine man's advertisement. 

The present edition of the National Formulary contains only 
formulas for the two basic preparations, " Liquid Petrox " and 
" Solid Petrox," but it is proposed to introduce in the forthcoming 
revision a full line of such formulas. This contribution to the sub^ 
ject is the result of an extensive series of experiments that we 
have carried out in order to determine proper formulas therefor. 
Most of the details of such experimentation and the failures are 
omitted and only formulas tried and in our opinion satisfactory 
are here presented. 

Neither the official nor the sub-titles should be unwieldy, but 
should be such as are euphonious and to become popular should 
lend themselves to the customary abbreviations of prescription writ- 
ing. The present N. F. Latin titles, " Petrolatum Saponatum 
Liquidum " and " Petrolatum Saponatum Spissum," are too long 
and cannot be readily abbreviated ; and these objections become more 
pronounced when added to a specific name, as in the compound 
preparations. Such could never be popularized and would detract 
from the use and usefulness of the formulas. 

The present N. F. has adopted as popular English title " Petrox," 
which precedes the British Codex title in publication and is already 
to some extent established in practice and must be retained at least 
as a popular title. It moreover lends itself easily to combined names 
for the compounds and it can likewise be readily Latinized into 
forms which are fairly euphonious. 

This class of preparations is distinctly different from all other 
official classes and is of sufficient importance to warrant the adoption 
of a distinguishing title. This leads to the suggestion that we adopt 
in the revision of the N. F. as the Latin title Petroxqlinum and 
synonyms Petroxolin and Petrox. In oider to demonstrate this 
point these terms and the compounds thereof are used throughout 
this paper. 

Anyone who has worked with oleates, knows how disagree- 
able and persistent is the odor of oleic acid. It is surprising that 
in this entire list of formulas as given in the Br. Ph. Codex and 
Erganzungsbuch and likewise as marketed by several manufacturers 
as proprietaries, there is no attempt to overcome this drawback to 
their use by the addition of a perfume. The addition of a small 



2l6 



Petrox Preparations. 



Am. Jour. Phann. 
May, 1911. 



amount of Oil of Lavender largely overcomes this objection and 
makes a decided improvement in the preparations and is an innova- 
tion that we should introduce. 

The compound preparations of this class are always listed as 
containing a definite percentage of the active medicament and for 
this reason as well as for the practicability of the work and to 
avoid the soiling of measures, the formulas submitted are all con- 
structed on a percentage basis and the ingredients are all weighed. 
This departure from our established rule of weighing solids and 
measuring liquids is for reasons quite apparent, preferable in this 
class. 

The N. F. directs the use of Spirit of Ammonia and the Br. 
Ph. Codex Ammoniated Alcohol 5 per cent, in some formulas and 
10 per cent, in others. Spirit of Ammonia is so rarely called for, 
that it is kept in stock by comparatively few druggists and even 
when in stock it is usually deteriorated and of uncertain strength. 
This led to experiments to determine if it could not in these formulas 
be replaced by ammonia water and alcohol. We found that this 
was feasible and have framed the formulas accordingly. 

Another point that needs emphasis, is, that while the " Liquid 
Petrox " will answer as the base for some of the medications or com- 
poundS;, it cannot be used alone as the base for the preparation of 
many of the important formulas. Such preparations as Iodine 
Petrox, 10 per cent., and Iodoform Petrox cannot be made by 
simple solution but the medicament must be incorporated by proper 
manipulation in the course of preparation. In others, the proportion 
of oleic acid or other ingredient must be somewhat modified to 
obtain perfect solution and a satisfactory product. 

The methods of manipulation as directed in the formulas, are 
those that were found necessary and it is quite important that these 
be carefully followed as deviation or careless manipulation may 
spoil the product. 



PETROXOLINUM LIQUIDUM. 



Liquid Petroxolin. 

Liquid Petrolatum 

Oleic Acid 

Oil of Lavender Flowers , 
Stronger Ammonia Water 
Alcohol 



Liquid Petrox. 



50 Gm. 



28 Gm. 

2 Gm. 

5 Gm. 
15 Gm. 



Am, Jour. Pharm. 1 
May, 1911. / 



Petrox Preparations. 



217 



Mix the Liquid Petrolatum, Oleic Acid and Oil o£ Lavender 
Flowers, in a flask, then add the Alcohol and finally the Stronger 
Ammonia Water and agitate thoroughly until clear, warming the 
mixture slightly, on a water bath if necessary. 

Slight warming may be required in cold weather, to promote 
the saponification. 

A yellowish-brown liquid, soluble in ether, chloroform, benzine 
and acetone, produces an emulsion on agitation with twice its 
volume of water. 

The proportion of the ingredients in this formula does not vary 
very greatly from that in the present N. F. formula. The product 
forms a permanent emulsion with water. The formula of the Br. 
Ph. Codex yields a preparation that will not even form a good 
temporary emulsion with water, but separates almost immediately. 

PETROXOLINUM CHLOROFORMI CAMPHORATUM. 

Camphorated Chloroform Petroxolin. 
Camphor and Chloroform Petrox. 

Chloroform. 25 Gm. 

Camphor 25 Gm. 

Liquid Petroxolin 50 Gm. 

Dissolve the Camphor in the Chloroform, then add the Liquid 
Petroxolin. 

PETROXOLINUM CADINI. 

Cade Petroxolin. Cade Petrox. 

Oil of Cade 25 Gm. 

Liquid Petroxolin 75 Gm. 

Mix them. 

PETROXOLINUM CRESOTI. 

Creosote Petroxolin. Creosote Petrox. 

Creosote 20 Gm. 

Oleic Acid 5 Gm. 

Liquid Petroxolin 75 Gm. 

Mix them. 

The Br. Ph. Codex directs the creosote formula to be only 5 
per cent, creosote, yet calls for 20 per cent, of guaiacol in the 
formula with the latter medication, but as the manufacturers list 



2l8 



Petrox Preparations. 



Am. Jour. Pharm. 
May, 1911. 



both as 20 per cent, formulas, it was deemed advisable to make 
our formulas correspond with the usage of American practice. If 
5 per cent., however, be adopted, then the addition of Oleic Acid 
will not be required in this formula. 

The Creosote, Guaiacol and Eucalyptol Petroxolins all darken 
considerably on keeping and if that is deemed to be an objection 
they can readily be prepared as wanted. The darkening is probably 
due to traces of iron in oleic acid and is not serious as it cannot 
affect the medicinal action. 

PETROXOLINUM EUCALYPTOLIS. 

Eucalyptol Petroxolin. Eucalyptol Petrox. 

Eucalyptol 20 Gm. 

Liquid Petroxolin 80 Gm. 

Mix them. 

PETROXOLINUM GUAIACOLIS. 

Guaiacol Petroxolin. Guaiacol Petrox. 

Guaiacol 20 Gm. 

Oleic Acid 5 Gm. 

Liquid Petroxolin 75 Gm. 

Mix them. 

PETROXOLINUM HYDRARGYRI. 

Mercury Petroxolin. Mercury Petrox. 

Mercury 30 Gm. 

Hydrous Wool-Fat 15 Gm. 

Solid Petroxolin 55 Gm. 

Triturate the Mercury with the Hydrous Wool-Fat until it is 
distributed and globules are no longer visible when examined with a 
lens magnifying ten diameters ; then add the Solid Petroxolin and 
mix thoroughly. 

The percentage of mercury has been reduced to 30 per cent., 
which in a base so readily absorbed is believed to be ample to 
produce salivation. 

PETROXOLINUM ICHTHYOLIS. 

Ichthyol Petroxolin. Ichthyol Petrox. 

Ichthyol 10 Gm. 

Oleic Acid 5 Gm. 

Liquid Petroxolin 85 Gm. 

Mix them. 



Am. Jour. Pharm > 
May, 1911. / 



Petrox Preparations. 



219 



PETROXOLINUM lODI. 

Iodine Petroxolin. Iodine Petrox 10 per cent. 



Iodine 10 Gm. 

Oleic Acid 40 Gm. 

Alcohol 20 Gm. 

Liquid Petrolatum 23 Gm. 

Oil of Lavender Flowers 2 Gm. 

Stronger Ammonia Water 5 Gm. 



Reduce the Iodine to a coarse powder by triturating in a mortar 
and transfer it to a suitable flask, add the Alcohol and then 
the Oleic Acid and agitate the contents of the flask until the Iodine 
is dissolved; now add the Oil of Lavender Flowers and the Liquid 
Petrolatum and mix the liquids and finally add the Stronger Water 
of Ammonia, shaking the mixture until a clear solution results. 

It was found impossible to prepare a 10 per cent. Iodine Petrox 
by simple solution in the liquid Petroxolin. By improper mixing 
there results another difficulty, namely, the separation out of the 
iodine as a salt, and this is a difficulty that has not been overcome 
by some of the manufacturers of the proprietaries. The writers 
have examined several bottles of one manufacture that is greatly 
prescribed in which appeared quite heavy crystalline sediments that 
proved to be ammonium iodide. A sample made by the proposed 
formula has now been kept for more than five months without 
sign of any separation of crystalline deposit. 



PETROXOLINUM lODI DILUTUM. 

Diluted Iodine Petroxolin. Iodine Petrox 5 per cent. 

Iodine Petroxolin 50 Gm. 

Liquid Petroxolin 50 Gm. 

Mix them. 

ALTERNATIVE FORMULA. 

Iodine in coarse powder 5 Gm. 

Liquid Petroxolin 95 Gm. 

Dissolve the Iodine by agitation with the Liquid Petroxolin in 
a stoppered bottle. 

An assay process should be provided for the Iodine Petroxolins. 

The Erganzungsbuch zum Deutschen Arzneibuch gives a 
method of assay which should, however, be thoroughly tried by 
competent chemists before adoption in the N. F, 



220 



Petrox Preparations. 



Am. Jour. Pharm. 
May, 1911. 



PETROXOLIN UM IODOFORM I. 



Iodoform Petroxolin. 



Iodoform Petrox. 



Iodoform 

Acetone 

Oleic Acid 

Eucalyptol 

Liquid Petroxolin 



3 Gm. 
20 Gm. 
10 Gm. 

3 Gm. 
64 Gm. 



Dissolve the Iodoform in the Acetone, add the Eucalyptol, Oleic 
Acid and the Liquid Petroxolin and mix the ingredients. 

Despite the statements in the books 3 per cent, of iodoform 
cannot be dissolved in Liquid Petrox alone ; even if heat be used, 
only a portion will dissolve and this largely crystallizes out on 
cooling. Consequently, one of the solvents for iodoform must be 
made use of and for this purpose we selected acetone. The dis- 
agreeable odor of iodoform is modified and largely overcome by 
the combination of eucalyptol and lavender. 



Dissolve the Menthol in the Liquid Petroxolin by agitation. 
The Br. Ph. Codex makes this only 2 per cent. ; we have 
followed the trade lists in making it 5 per cent. 

PETROXOLINUM METHYLIS SALICYLATIS. 

Methyl Salicylate Petroxolin. Methyl Salicylate Petrox. 

Methyl Salicylate 20 Gm. 

Liquid Petroxolin 80 Gm. 



PETROXOLINUM MENTHOLIS. 



Menthol Petroxolin. 



Menthol Petrox. 



Menthol 

Liquid Petroxolin 



5 Gm. 

95 Gm. 



PETROXOLINUM NAPHTHOLIS. 



Naphthol Petroxolin. 

Betanaphthol 

Liquid Petroxolin . . . , 



Naphthol Petrox. 

10 Gm. 

90 Gm. 



Dissolve the Betanaphthol in the Liquid Petroxolin by agitation. 



Am. Jour. Pharm. ) 
May, 1911. / 



Petrox Preparations. 



221 



PETROXOLINUM PHENOLIS. 

Phenol Petroxolin. Phenol Petrox. 

Phenol 5 Gm. 

Liquid Petroxolin 95 Gm. 

Dissolve the Phenol in the Liquid Petroxolin by agitation in 
a stoppered bottle. 

PETROXOLINUM PICIS. 

Tar Petroxolin. Tar Petrox. 

Oil of Tar 25 Gm. 

Liquid Petroxolin 75 Gm. 

Mix them. 

Oil of tar makes a clear solution and for this use it is certainly 
to be preferred to tar. Hence we have thus modified the formula 
of the foreign formularies which direct tar. 

PETROXOLINUM SALICYLATUM. 

Salicylated Petroxolin. Salicylated Petrox. 

Salicylic Acid 10 Gm. 

Oleic Acid 5 Gm. 

Liquid Petroxolin . 85 Gm. 

Dissolve the Salicylic Acid in the Oleic Acid and Liquid 
Petroxolin. 

PETROXOLINUM PHENOLIS CAMPHORATUM. 

Camphorated Phenol Petroxolin. Camphorated Phenol Petrox. 
Campho-Phenic Petrox. 

Phenol 12.5 Gm. 

Camphor, in powder 37.5 Gm. 

Liquid Petroxolin 50.0 Gm. 

Mix the Camphor and Phenol and when the mixture has liquefied 
add the Liquid Petroxolin and mix thoroughly. 

PETROXOLINUM SULPHURIS. 

Sulphur Petroxolin. Sulphur Petrox. 

Sublimed Sulphur 3 Gm. 

Linseed Oil 37 Gm. 

Oleic Acid 30 Gm. 

Liquid Petroxolin, sufficient quantity to make 100 Gm. 



222 



Petrox Preparations. 



Am. Jour. Pharm. 
May, 1911. 



Heat the Sublimed Sulphur and Linseed Oil in a flask, on a 
sand bath, until the sulphur is dissolved, then allow to cool and 
add the Oleic Acid and sufficient Liquid Petroxolin to make the 
product weigh lOO grammes, warming the mixture slightly if neces- 
sary to obtain a clear liquid. 

A dark brown, thick, oleaginous liquid possessing a very foul 
odor. By itself it is not apt to be applied to humans in this life, 
but it can be diluted and serves for the preparation of the succeed- 
ing formula. 

PETROXOLINUM SULPHURIS COMPOSITUM. 

Compound Sulphur Petroxolin. Compound Sulphur Petrox. 

Sulphur Petroxolin lo Gm. 

Oil of Cade lo Gm. 

Thymol 3 Gm. 

Eucalyptol 3. Gm. 

Oil of Turpentine 30 Gm. 

Liquid Petroxolin, sufficient quantity to make 100 Gm. 

Mix the Thymol and Eucalyptol, add the Oils and then the 
Sulphur Petroxolin and finally sufficient Liquid Petroxolin to 
make the product weigh 100 Grammes. 

PETROXOLINUM TEREBINTHIN^ VENET^. 

Venice Turpentine Petroxolin. Venice Turpentine Petrox. 

Venice Turpentine 20 Gm. 

Liquid Petroxolin 80 Gm. 

Mix them. 

PETROXOLINUM SPISSUM. 

Solid Petroxolin. Solid Petrox. 

Paraffin 37 Gm. 

Liquid Petrolatum 20 Gm. 

Oleic Acid 30 Gm. 

Oil of Lavender Flowers 3 Gm. 

Alcohol 5 Gm. 

Stronger Ammonia Water 5 Gm. 

Melt the Paraffin with the Liquid Petrolatum, on a water bath, 
add the Oleic Acid, and transfer the mixture at once to a warm 
mortar; immediately add the Oil of Lavender Flowers and the 
mixed Alcohol and Stronger Ammonia Water and stir continuously 
until cool. 



Am. Jour. Pharm. 
May, 1911. 



Petroxolin Spissum. 



223 



This yields a smooth pale-yellow ointment and if the above 
directions are carefully followed the resulting product is smooth 
and creamy, very suitable as an ointment base. It is essential that 
the mortar be warmed so as to insure a gradual cooling and that 
the stirring be continuous, otherwise the mass will be uneven and 
granular. 



PETROXOLINUM SPISSUM. 

THICK OR SOLID PETROXOLIN OR PETROX. 

By Otto Raubenheimer. 

As this preparation possesses the property of taking up at least 
twice its weight of aqueous liquids, a point which should be strongly 
emphasized in the propaganda, I believe it should therefore be of 
a hard consistency, rather than creamy. 

One of the ingredients in this preparation also and again demon- 
strates the necessity, that, in order to avoid confusion, not only 
the potent medicaments, but all articles of the same official title in 
the various pharmacopoeias of the world should be identical as to 
quality, purity and strength. 

I refer to Paraffin, which, according to U.S.P., VIII, has a 
M.P. 51-57° C. and as low as 46° in some commercial samples, but 
which, according to D.A.B., IV, has a M.P. 74-80°, and which was 
reduced to 68°-72° in the 5th edition just published. 

The U.S. P. product is a petroleum paraffin while the German 
pharmacopoeial product is a refined earth wax or ceresin, entirely 
different in physical and even chemical characteristics. 

As the origin of Vasogen, etc., can be traced to the " Vaterland," 
therefore the German paraffin or ceresin should undoubtedly be 
used. 

Having made numerous experiments with Solid Petrox, I here- 
with present three samples together with formulas : 





No. I. 


No. 2. 


No. 3. 




30 


40 




(Ceresin 4 P. = 24 


gm. 


Liquid petrolat . . . 


22 


20 


Ung. paraffin 60 


j Wool-fat I P. = 6 


gm. 




35 


27 


27 


( Liq. petrol. 5 P. =30 


gm. 


Oil la vend, flow . . 


3 


3 


3 




5 


5 


5 






Strong am. wat. . . 


5 


5 


5 








100 


100 


100 


gm. 





224 German Pharmacopoeia Requirements. { ^""May ^wi*^* 

No. I is Beringer's Formula, substituting or better replacing 
paraffin with ceresin. 

In No. 2 I increased ceresin to 40 (from 30) and decreased 
Oleic Acid to 27 (from 35) and Liquid Petrolatum to 20 (from 
22). 

Its harder consistency makes it better adapted for use during 
the hot weather. 

In No. 3, I have employed what I consider an ideal hard oint- 
ment base, namely Ung. Paraffini or durum of the D. A. B. V. 
(ceresin 4, liquid petrolatum 5, and wool-fat i part). 

No special precautions were taken with any of these samples, 
excepting melting on water-bath of ceresin, liquid petrolatum and 
oleic acid, the addition of the other ingredients and cooling without 
stirring. 

In my opinion the description of Solid Petrox in N. F., IV, 
should state something' like the following : 

A yellowish ointment, capable of absorbing at least two parts 
of water." 

Brooklyn, N. Y., March 19, 191 1. 



THE GENERAL REQUIREMENTS OF THE GERMAN 
PHARMACOPCEIA (V)* 

By G. a. Menge. 

To make exhaustive and critical comment upon all of the general 
requirements of the new German Pharmacopoeia would require 
more time, and tax your patience to a greater degree, than should 
be tolerated in a minor detail of your program. Therefore, except 
for some very general features to which it seems to me your 
attention should be directed at this time, I shall limit my specific 
discussion to those general requirements which apply to the de- 
termination of melting points, freezing points and boiling points. 

You are doubtless familiar with the practice, as applied in the 
old edition of the German Pharmacopoeia, of incorporating in the 
introductory part more or less specific directions covering general 



♦Read at the March meeting of the Washington branch of the A. Ph. A. 



^'"'Mry^im*'^"'' } G^'^^^^CL'y^ Pharmacopoeia Requirements. 225 

methods and procedure required in determining physical constants, 
analytical data^ etc., and also specific definitions of general terms 
used in the body of the book — such as coarse, medium and fine 
(pieces or powder), room temperature, unweighable residue, soluble 
and insoluble, etc. 

This feature of the old edition has not only been continued 
but has been extended and improved in the new. The advantage 
— from several viewpoints — of such a special treatment of general 
methods, terms and other details, seems to me to be obviously very 
great, and in principle at least should be adopted in the pending 
revision of the United States Pharmacopoeia. 

In this connection it is to be noted that for the sterilization of 
any substances that may require such treatment, the requirement 
in both the old and the new editions of the German Pharmacopoeia 
is a very general one, consisting merely in the statement that 
unless otherwise stated, sterilization is accomplished by the appli- 
cation of heat in accordance with the rules of bacteriological technic, 
giving due regard to the properties of the substance to be sterilized. 
Obviously real compliance with such a general requirement neces- 
sitates some training in the essential principles of bacteriology as 
applied to sterilization. It is intended, I believe, that the new 
United States Pharmacopoeia shall include some requirement on 
sterilization. It is plain that either our requirement must be much 
more specific than the German — probably impractically so — or the 
training in pharmaceutical schools and colleges should include at 
least enough bacteriology to cover such a requirement. 

The methods and procedure for the determination of the melt- 
ing points, freezing points, and boiling points of pharmacopoeia! 
substances as prescribed in this new edition, seem to me to repre- 
sent both progress and retrogression — though the former doubtless 
predominates. In the attempt to justify this general conclusion, 
permit me to briefly contrast the old and the new requirements 
and to offer comment upon certain details : 

In both the old and the new editions the melting point re- 
quirements, as to methods and procedure described in the introduc- 
tory chapter, are divided into two parts ; the first part applying 
to all pharmacopoeial products except the fats and fatty substances, 
and the second part to the fats and fatty substances. 

In the old edition the requirements for compounds of the first 
class provide the following details : Dry the sample in a desiccator 



226 German Pharmacopoeia Requirements. {^™May^9ii*'"* 

over sulphuric acid for 24 hours. Introduce sufficient of the dry 
sample into a capillary tube of i mm. diameter to form a column 
2-3 mm. high in the bottom of the tube. Attach the tube so charged 
to a suitable thermometer and immerse in a bath of sulphuric acid 
contained in a test tube of 30 mm. diameter. Heat gradually with 
frequent stirring. That temperature at which the opaque mass 
becomes a transparent liquid and flows together in transparent 
drops is regarded as the melting point. 

In the corresponding requirements of the new edition, im- 
provement is noted in the following details : 

1. Beside the same period and method of drying, the sample 
is required to be " finely divided " ; and as previously noted this 
degree of fineness is specifically defined in another paragraph. 

2. The column of sample in the bottom of the capillary must 
be 2-3 mm. high when tapped down." 

3. The position of the sample with reference to the bulb of the 
thermometer is definitely defined. 

4. A most important improvement, as I see it, is noted in the 
matter of heating the bath — against no provision on this detail 
in the old edition, the new edition provides that from a point 10° 
below the assumed melting point, the rise in temperature shall be 
at the rate of 2° per minute. 

The period and manner of drying is the same " when not other- 
wise stated," and the definition of melting point is the same. 

The most radical change (and one which in my opinion is a 
step backward) is found in the method applied. The new method 
requires apparatus which is a cross between the Roth apparatus 
and the Graebe apparatus without including the specific advantage 
of either. It consists of a test tube 15 mm. in diameter and 30 
cm. long, containing sulphuric acid to a depth of 5 cm., and ad- 
justed in the neck of a round bottomed bulb of 80-100 cc. capacity 
having a neck about 20 cm. long, and 3 cm. in diameter, and con- 
taining sufficient sulphuric acid to two-thirds fill the neck when the 
test tube is in place. 

The most serious defect in the new method, as I see it, is the 
absence of stirring, a detail which I consider essential to a well 
controlled melting point determination, and which is not easily 
applied with such a double bath apparatus. In this detail, therefore, 
I feel that the new requirements constitute a definite retrogression 
as compared with the old. 



^^'£y^'im!"^'} German Pharmacopoeia Requirements. 227 

It seems to me also that in the matter of definition of the melting 
point the book leaves a large opening for progress toward more 
rational and adequate pharmacopoeial standardization. I am firmly 
of the opinion that the requirement of a definite melting interval 
or range rather than a melting point, would establish a more 
logical and effective standard. 

The old requirements for the fats and fatty substances involve 
the use of a thin-walled capillary tube of not more than i mm. 
diameter, open at both ends. Enough of the melted fat is drawn 
into one end of the tube to form a column about i cm. high, and 
is then cooled at 10° for 24 hours to insure complete solidification. 
Attached to suitable thermometer the sample is immersed in water 
contained in a test tube of 30 mm. diameter. The bath is gradually 
warmed with frequent stirring. The temperature at which the fat 
becomes transparent and rises in the tube is the melting point. 

The new requirements differ in the following details: 

1. A U-shaped capillary of 0.5-1 mm. diameter, filled with 
molten fat to the same level in each arm replaces the straight tube. 

2. The sample is cooled on ice for 2 hours, or at 10° for 24 
hours. 

3. The charged tube is attached to a suitable thermometer so 
that the sample will be on a level with the thermometer bulb. 

4. A bath of equal parts of glycerin and water displaces the 
bath of sulphuric acid. 

5. Temperature must be raised " very slowly " to avoid super- 
heating. 

6. That temperature at whjch the fat becomes perfectly clear 
and transparent is the melting point. 

I am of the tentative opinion that the U-capillary is not an 
improvement over the straight capillary in determining the melting 
point of fats. This constant is generally more difficult of exact 
determination as applied to fats than for the other class of com- 
pounds. It is claimed by authorities on fats that some fats become 
clear and transparent before complete melting while others remain 
cloudy for some time after, and therefore perfect clearness and 
transparency is not a good criterion of the melting point. For 
the purpose of pharmacopoeial standardization, however, the main 
thing, it seems to me, is to select some behavior, in the region of 
the much mooted " true melting point/' which is easily observed 
and reasonably constant. With the old method, the rise of the 



228 German Pharmacopoeia Requirements. {'^"' Viariyii**'"' 

fat in the tube under the sHght pressure of the water would seem 
to fulfill such a condition and to indicate at least the melting point 
of that portion of the fat which is in direct contact with the tube. 
More extended experience with fats might of course change my 
views on this point. 

The absence of stirring as a requirement in these determinations, 
although perhaps not so serious an omission as for melting points 
at higher temperature, still seems to me a mistake. 

The requirement in the new edition of a method for the determina- 
tion of freezing points is all on the credit side — no such requirement 
being found in the old edition. The method is substantially as 
follows: Ten grams of the substance under investigation are care- 
fully melted in a test tube containing a suitable thermometer. By 
dipping the tube in water, the temperature of which is about 5° 
C. below the freezing point of the substance, the melt is cooled 
to about 2° below the freezing point; then by stirring with the 
thermometer, or if necessary by seeding with a small crystal of the 
substance under investigation, freezing is induced and the highest 
temperature observed during the freezing process is the freezing 
point. 

The method has the advantage of extreme simplicity, and is 
therefore readily available to all concerned. It is also probably 
adequate for the purpose intended, but without personal experience 
with the method I hesitate to offer critical comment, except per- 
haps that the dimensions of the test tube, and also of the ther- 
mometer, used should be specified. The latter criticism is oi 
general application and will be referred to later. 

Just as for the freezing point, the methods described for the 
determination of the boiling point constitute a feature of the new 
edition not found in the old, and therefore represent a distinct 
advance in standardization. 

As in the case of the melting point, the boiling point require- 
ments are divided into 2 parts : 

The first part describes a method which is intended to serve 
only as a means of identification of the liquid, and not as a test 
of its purity. The procedure is somewhat similar to that described 
for the first melting point method. A thin-walled capillary tube 
of 3 mm. internal diameter and containing 1-2 drops of the liquid 
under investigation is attached to a suitable thermometer and im- 
mersed in a bath of sulphuric acid just as in the first melting- 



"^""'May ^911*^™' I German Pharmacopoeia Requirements, 229 

point method. A second capillary tube open at the lower end and 
sealed about 2 mm. above the open end dips into the liquid in the 
main capillary to prevent bumping. The temperature at which 
an unbroken series of bubbles begins to rise from the bottom of the 
liquid is the boiling point. 

Having had no experience with this or a similar method I 
offer no critical comment. 

The second boiling point method described is intended to deter- 
mine the purity of the liquid and of course involves distillation. 
It is required that at least 50 c.c. of the substance be distilled 
from a distilling flask of 75-80 c.c. capacity. The bulb of the 
thermometer must be placed i cm. below the delivery tube of the 
flask. Before beginning distillation a small piece of broken porce- 
lain is placed in the liquid tO' prevent bumping. The flask is heated 
in an air bath. Nearly the entire liquid must distill over within 
the required temperature — any low boiling fraction and any residue 
should be only very small. 

It seems to me that this method might be improved by being 
more specific in detail ; for instance, the length and diameter of the 
neck of the flask and the position of the delivery tube with relation 
to the mouth of the flask should be defined. Also such indefinite 
phraseology as nearly " and very small " are surely out of place 
in the standardization of a physical constant. It would seem 
feasible, instead, to incorporate in the description of individual 
liquids a percentage yield of distillate that should be obtained within 
the required limits of temperature ; or to have a general percentage- 
yield requirement, applied to all liquids unless otherwise stated." 

Finally: I consider that the general requirements covering 
melting points, freezing points and boiling points, are seri- 
ously deficient in the lack of more specific limitations re- 
garding the thermometer to be used. The book uniformly pre- 
scribes the use of einem' geeigneten Thermometer " — a phrase, 
which I have translated " a suitable thermometer/' although pos- 
sibly it could with equal accuracy be interpreted to mean " an 
accurate thermometer." In either case, however, my criticism 
applies, with little variation. Much argument might be ofifered to 
justify my attitude on this point — a single illustration I believe 
will serve the purpose : Of two equally accurate thermometers, 
standardized in the same way and covering the same range, one 
might be six inches long and the other three feet long — obviously 



230 Philadelphia College of Pharmacy. ]^'"-May'i9ii*"° 

direct observations of the same melting point with the two ther- 
mometers registering near their upper Hmits would be widely 
divergent. I am firmly convinced that if we are to approach real 
standardization of these physical constants, the pharmacppoeial 
requirements must include either the use of a standardized ther- 
mometer with application of correction for emergent stem, or the 
use of a perfectly uniform standardized thermometer {i.e., an 
official thermometer). In the latter case the emergent stem cor- 
rection might be omitted without effect on standardization, but with 
sacrifice of the greatest accuracy. 

Note. — Much more extended and detailed discussion of melting- 
point requirements, as applied to the United States Pharmacopoeia, 
will be found in Hygienic Laboratory Bulletin 70, of the Public 
Health and Marine Hospital Service. 



PHILADELPHIA COLLEGE OF PHARMACY. 

ANNUAL MEETING. 

The annual meeting of the College was held March 27th, 191 1, 
at 4 P.M. in the Library. In the absence of President French on 
account of illness, the First Vice-President, Dr. Richard V. Mat- 
tison, presided. Thirty-one members were present. The minutes 
of the quarterly meeting held December 27th, 19 10, were read and 
approved. The minutes of the Board of Trustees for the meetings 
held December 6th, 1910, January 3rd and 25th and February 7th, 
191 1, were read by the Registrar, J. S. Beetem, and approved. 

The Annual Report of President French was read by the Secre- 
tary and ordered entered on the minutes. The following items of 
information are abstracted from the Report: 

The property as a whole is in good condition. The furnaces and 
engines have been repaired putting the heat and light plant in first class 
condition. Improvements have been made in the Pharmaceutical Labora- 
tory, adding materially to the convenience of the teaching force and to 
that of the Students, and greatly facilitating the increased work of the 
department. The ceiling between the fifth floor and attic of the Tenth 
Street building was torn out so as to convert the room into a Gymnasium, 
giving splendid ventilation and enabling the Board of Trustees to estab- 
lish a high grade Modern Gymnasium. The alterations in the Pharma- 
ceutical Laboratory and the establishment of a Gymnasium cost $216672. 



^"*May,'"i9n"'""'} Philadelphia College of Pharmacy. 231 

The department of Physical Training has proven of benefit to the Student 
body. Many Physical defects existing, especially those of the eyes, ears 
and throat have been corrected, and the systematic exercises given to the 
classes has added much to the health and comfort of the Students. 
The total number of Students enrolled v^as 515. 

In the Chemical Laboratory ninety-one students are doing individ- 
ual work, and seventeen, thesis work. There have been twenty-five special 
chemistry students during the year. Twenty third-year students are 
doing thesis work in the Pharmaceutical Laboratory. There are twelve 
students in Bacteriology, and also some carrying on special investigations. 

The Department of Botany and Pharmacognosy has made material 
progress during the year, but unfortunately is much crowded and badly 
in need of more room to extend their work. One of the most valuable 
adjuncts is the greenhouse and botanic gardens on the roof of the Annex 
building. The students derive much benefit from the same. The grow- 
ing plants are used for class instructions, and are utilized for special 
investigations. Inquiries from various parts of the country are not in- 
frequent regarding the conditions for growing medicinal plants, and it 
is gratifying to those in charge to be able to supply this information. 

The Pharmaceutical, Chemical and Analytical Laboratories are now 
over-crowded, the Annex building on Cherry street gave temporary relief, 
but the growing demands of the classes are now so great that it seems 
necessary that increased accommodations be secured in the near future. 
The College location was originally a residential section, but with the 
lapse of years it is now surrounded by manufacturing establishments 
which must necessarily imperil the historic Collections in the building. 
These collections if lost could never be replaced — they possess a world 
wide reputation, and it is the urgent duty of your organization to pre- 
serve them for future generations. With this thought in mind your 
President has for three years past been endeavoring to secure from the 
City of Philadelphia a site for a new building, and it is hoped that in the 
near future this may be secured. 

The Treasurer will report a material increase of the balance in bank 
over last year. 

It is now a matter of record that the College Bulletin and Alumni 
Report have been merged and the first volume of Number Four was 
issued February 191 1 under the Style of ''Bulletin of the Philadelphia 
College of Pharmacy and Alumni Report." 

Two members were elected during the year. Four of our members 
have died during the past year, namely : Dr. Louis G. Bauer, David W. 
Ross, David Jamison and Caleb R. Keeney. 

The Ninetieth Anniversary of the College occurred on February 23. 
191 1, at which time hearty congratulations were received from a number 
of the scientific and educational institutions of the city, and your Presi- 
dent wishes to extend to those institutions, their officers and faculty 
his appreciation of their kindly thought, and also to his fellow officers. 
Board of Trustees and Faculty for their hearty support and co-operation 
during the year. 



232 Philadelphia College of Pharmacy. {^"^■^ly'-Jn^"'^- 

REPORTS OF COMMITTEES. 

Committee on Pharmaceutical Meetings. — The meetings have 
been held regularly, and the programs while not as full as hereto- 
fore, have been excellent. Various members presided at the meetings. 
At the April meeting a most interesting discussion took place on 
Anti-Narcotic legislation which was participated in by many of the 
members — it was one of the best attended meetings of the entire 
series. The May meeting was given over to a symposium by 
students on their theses. This precedent is a good one, as the papers 
presented show what the apprentices are capable of doing and that 
the future of our profession will be taken care of. At the succeed- 
ing meetings, among those presenting papers were Dr. E. R. Larned 
of the University of Buffalo, C. Mahlon Kline, Professor H. C. 
Wood, Jr., George M. Beringer, Jr., and George M. Beringer. 

The November meeting was given over to the memorial exer- 
cises in connection with the presentation of a portrait of Dr. Susan 
Hayhurst, the first woman graduate of the College. 

The Committee thinks it is safe to say that every retail pharma- 
cist would have saved much valuable time if he were present to 
have seen the demonstrations in connection with the papers which 
were read, and it is to be regretted that more do not appreciate 
the economy of time that results by attending these meetings and 
that of other associations where papers are read and discussions held. 

Publication Committee. The American Journal of Pharmacy 
has been issued regularly during the year. There is an increase 
in the amount received from subscribers and advertisers, and a 
decrease in the expenses from last year. The old book with the 
names and records of subscribers which has been used for fifty 
years, has been replaced by the modern index system. This book 
is of considerable historic interest and will be placed in the College 
Collection with the other historic material. 

Colleges, Universities, Libraries, and manufacturing laboratories 
are being constantly added to our list of subscribers, showing that 
the subscription list is becoming more stable. 

Editor's Report. The matter published in The American 
Journal of Pharmacy during the past year may be classified as 
follows : Fifty-four original and selected articles which may be 
subdivided as follows : two Chemical, twenty-five Pharmaceutical, 



^""■Marisif'"" } Philadelphia College of Pharmacy. 233 

two pharmacognostical, six technical, three on biological standard- 
ization and sixteen on miscellaneous subjects, quarterly reviews in 
progress of Pharmacy; thirty-one book reviews; a symposium on 
maceration and percolation, eight notes from correspondents, also 
reports of the United States Pharmacopoeial Convention, the annual 
meeting of the American Pharmaceutical Association, the National 
Wholesale Druggists Association, the American Conference of 
Pharmaceutical Faculties, the Tenth International Pharmacopoeial 
Congress, Minutes of the College meetings. Minutes of the Board 
of Trustees and pharmaceutical meetings, abstracts of special 
lectures, memorial and obituary notes, abstracts and miscellaneous 
notes. 

The most notable feature of the Journal the past year has been 
the large number of papers dealing with methods and standards 
of the United States Pharmacopoeia, many of these papers were 
contributed by the chemists of the U. S. Public Health and Marine 
Hospital Service. Without enumerating more of these papers it 
may be said that they are of an unusually high order of merit and 
will no doubt be widely consulted. 

Curator's Report. The question of the identity of drugs has 
become a most important question, because the dealer guarantees 
the identity of the drugs sold, according to certain standards, or 
suffer legal penalties if the goods be improperly branded. For this 
reason it has become essential that specimens of drugs of doubtful 
identity, either wholly or in part, must be compared with specimens 
of undoubted genuineness. For this purpose standard specimens 
of drugs are most necessary, and it may be fairly claimed that the 
drug collections of the Philadelphia College of Pharmacy are prob- 
ably the best of their kind in this country. These collections are 
of undoubted authenticity and are rare and valuable. They are 
being consulted more and more by the pharmaceutical public and 
to make them more valuable an endeavor should be made to cover 
the entire field of vegetable drugs, every genera and species and 
varieties of plants having medicinal value should be added to the 
collections. Such a collection would be of immense value for refer- 
ence not only to retail, wholesale and manufacturing pharmacists, 
but also to government authorities in their legal prosecutions. 

Librarian's Report. The Library Committee has gone to con- 
siderable expense for re-organization. Fifteen hundred books have 



234 Philadelphia College of Pharmacy. 

been stamped and marked with the Library ownership, classified, 
accessioned and shelf listed. 

The collection of Pharmacopoeias has been brought up to date. 
New editions of the German, Austrian, Hungarian, Belgian, Swiss, 
Swedish, Norwegian, Dutch, Russian, Spanish, Italian and Japanese 
have been added. Since the first of January five hundred and 
twenty-eight persons have consulted the Library. 

The resignation of William Ogilby from active membership was 
presented, and accepted with regret. 

Professor Kraemer presented an enlarged photograph of the 
late Doctor Susan Hayhurst (the first woman graduate of the 
College) which had been donated by Mr. F. Gutekunst. The thanks 
of the College were tendered the donor. 

The Committee on By-Laws was re-appointed: George M. 
Beringer, Joseph W. England, C. A. Weidemann. 

The report of the Committee on Nominations were received and 
ordered entered and filed. 

The election of officers, committees and trustees followed, Messrs. 
William Mclntyre and E. M. Boring being appointed tellers. A 
ballot being taken the tellers reported the result when the following 
were declared elected. 

President, Howard B. French ; First Vice-President, Dr. Richard 
V. Mattison; Second Vice-President, Joseph L. Lemberger; Cor- 
responding Secretary, Dr. A. W. Miller; Recording Secretary, 
C. A. Weidemann ; Treasurer, Richard M. Shoemaker ; Curator, 
Joseph W. England ; Editor, Henry Kraemer ; Librarian, Kather- 
ine E. Nagle. 

Trustees for three years : Joseph P. Remington, C. Carroll 
Meyer, and C. Stanley French. 

Committee on Publication: Samuel P. Sadler, Henry Kraemer, 
Joseph W. England, Joseph P. Remington, M. I. Wilbert, Miss 
Florence Yaple and Charles H. La Wall. 

Committee on Pharmaceutical Meetings: Henry Kraemer, 
Joseph P. Remington, C. B. Lowe, W. L. ClifTe and William 
Mclntyre. 

President French made the following appointments: Delegates 
to New Jersey Pharmaceutical Association ; George M. Beringer, 
Henry Kraemer, C. B. Lowe, H. L. Stiles and H. P. Thorn. 

Delegates to Pennsylvania Pharmaceutical Association : C. B. 
Lowe, Joseph P. Remington, F. P. Stroup, William Mclntyre, 



'^°' Mayri9ii*'°' } Philadelphia College of Pharmacy, 235 

Jacob M. Baer, William E. Lee, Charles Leedom, E. F. Cook, Samuel 
C. Henry and Clemmons Parrish. 

Committee on Hallberg Memorial: F. P. Stroup, H. K. Mul- 
ford, W. L. Cliffe. 

. C. A. Weidemann, M.D., 

Recording Secretary. 

ABSTRACT FROM THE MINUTES OF THE BOARD OF TRUSTEES. 

Dec. 6, 19 10. — Fourteen members present. Committee on 
Library reported between six and seven hundred books had been 
classified, accessioned and shelf-listed. Five books were donated 
during the month. Committee on Instruction reported that Pro- 
fessor Kraemer had recommended Mr. Armin Kohl Lobeck for the 
position of Instructor in Botany, his duties to begin on June ist, 
191 1. The recommendation of the Committee was approved and 
Mr. Lobeck elected to fill the position. Committee on Discipline 
reported that a first-year student had presented a false certificate for 
entrance. After a thorough investigation, the young man, to- 
gether with his preceptor, were found guilty, and the student was 
dismissed and informed that he could never again be admitted as 
a student in the College. Alumni Committee reported that the 
subject of amalgamating the ''Bulletin'' with the ''Alumni Re- 
port" had been under consideration by the Board of Directors of 
the Alumni Association, and as a result of their deliberations, they 
would recommend a merger of the two publications under certain 
conditions. After a full discussion by the members of the Board, 
the Report of the Committee was adopted. Committee on Athletics 
reported that the Gymnasium was completed with an expenditure 
for total equipment, alterations, etc., much less than had at first 
been anticipated. Miss Katharine E. Nagle, the Acting Librarian, 
was elected to active membership in the College. The Dean 
presented, on behalf of Mr. H. L. Tomkinson, an interesting docu- 
ment in the shape of a bill for professional services by Doctor 
Lloyd Zachary, covering a period from October, 1746, to November, 
1753, and, on motion, a vote of thanks was tendered the donor. 

Jan. 3, 191 1. — Committee on Library reported that one thousand 
books had been accessioned and shelf-listed since October, 1910. 
Several foreign Pharmacopoeias recently issued have been pur- 
chased and others ordered to bring our collection of Pharmacopoeias 
up to date. Mr. England, for the Committee on Resolutions in. 



236 Philadelphia College of Pharmacy. { ^""M^risii 

memory of Professor Hallberg, submitted and read same, which 
were unanimously adopted and an engrossed copy ordered to be 
sent to the family. 

Feb. 7, 191 1. — Sixteen members present. Committee on Library 
reported three hundred and eighty-seven books accessioned since 
last report. During the past month a number of books were 
donated. Eighty-one persons had consulted the Library during 
the month. Committee on Examinations reported that J. Harry 
Swain had successfully passed his examinations of Proficiency 
in Chemistry/' when, on motion, it was ordered that the Certificate 
be granted. Committee on Announcement reported the merger of 
the Bulletin and the Ahnnni Report. The new issue will be pub- 
lished bi-monthly and will contain no advertisements, but will Lave 
matters of interest to the graduates and students of the College. 
It will be sent to all the graduates of the College without charge. 
Upon invitation, the Board took a recess and visited the Gymnasium 
tO' witness a drill by one of the class sections. The president 
stated that on the 23d of February, 191 1, ninety years have elapsed 
since the founding of the College, and it was his pleasure to extend 
to the Board of Trustees, the Faculty and the Instructors of the 
College, an invitation to take dinner in celebration of the anniver- 
sary, with him at the Union League, on the evening of February 23, 
191 1. The invitation was accepted and a vote of thanks extended 
to Mr. French. A letter was received from Mr. Walter E. Martz, 
Executor of the Will of the late George W. Hayes, reciting a 
clause in the Will of Mr. Hayes as follows : " I direct that my gold 
watch be given to the graduate in chemistry and pharmacy of the 
Philadelphia College of Pharmacy, who is truly worthy, and who 
graduates with the highest honors from the said institution, after 
my departure." Mr. Hayes received this watch as a prize from 
the College in 1880. It was moved that Mr. Martz be notified that 
the College would accept the gift and award the same in accordance 
with the Will. By resolution of the Board, it was directed that 
an inventory of the Fixtures, Contents, etc., of the College, be 
taken as would be useful in the event of loss by fire. After a gen- 
eral discussion, it was decided that the heads of Departments and 
their assistants be requested to begin at their earliest convenience 
iQ make such an inventory. 

C. A. Weidemann, M.D., 

Recording Secretary. 



^'"*MaTi9i^'"'""} Philadelphia College of Pharmacy. 237 

PRESENTATION OF PORTRAIT OF THE PRESIDENT, 
HOWARD B. FRENCH, PH. G. 

Seldom has the writer had the privilege to be present on such a 
felicitous occasion as Tuesday evening, April 4, 191 1, at the 
Union League, when a most excellent life-size oil portrait of Presi- 
dent French was presented to the College on behalf of the officers, 
faculty, members of the Board of Trustees, members of the College 
and Alumni Association. The occasion was one of the great events 
in the history of the College, and was commemorated by a dinner, 
which was participated in by not only many of those who had con- 
tributed tO' the fund, but by the Mayor of Philadelphia, the State 
Superintendent of Education and other officials. 

The portrait of President French is of him in his academic 
gown with cap in hand and was painted by Mr. Hugh H. Brecken- 
ridge, a teacher in the Academy of Fine Arts of Philadelphia, 
and an artist of high standing, particularly by reason of his ex- 
cellent work in portraiture. The portrait occupied a central position 
in the brilliantly lighted banquet hall, which was resplendent with 
floral and other decorations in which the College and national colors 
were conspicuous. President French, though suffering from a cold, 
was present, and remained during the greater part of the cere- 
monies. The menu contained a four-color reproduction of the 
portrait and will be treasured as an excellent souvenir of the 
occasion. The addresses were in the nature of personal tributes 
to President French for his zealous and efficient labors as a man 
of affairs, as a leading citizen in the civic life of Philadelphia, and 
Pennsylvania, and as president of one of the oldest educational 
institutions in America. 

Prof. Joseiph P. Remington acted as' 'toast-master. In his 
opening remarks he alluded to the fact that those assembled had 
met tO' do honor to Mr. Howard B. French, President of the 
Philadelphia College of Pharmacy, who had not only done much 
for the College of Pharmacy, but for the City of Philadelphia. 

The portrait was presented on behalf of the members and 
alumni by Mr. George M. Beringer, A.M., Ph.M., Chairman of the 
Committee on President French Portrait, and also Chairman of 
the Board of Trustees of the College. 



238 Philadelphia College of Pharmacy. { ^""•Mar'mi*™ 

presentation address by mr. beringer. 

Mr. Toastmaster, Honored Guests, Friends and Fellow 
Alumni : 

This is a memorable occasion in the history of the Philadelphia 
College of Pharmacy. Although she has attained the mature age 
of 90 years, one will search her records in vain for a similar 
event, and with the modesty that has always characterized her 
career she to-day pleads first offense." 

Heretofore, the alumni and members of the College, possibly 
because of the conservatism inherited from the Quaker founders, 
have refrained from giving any similar public testimony to the 
worth and appreciation of the services of any of her many faithful 
officers, during their existence in the flesh, but have been contented 
to have them await encomiums and merited recognition in obituary 
notices and with the rewards of the hereafter. On this occasion we 
have made a notable and universally approved departure from the 
time honored traditions and customs of the institution. 

Do not think that I am going to use this as a proper premise 
to deduce the conclusion that institutions, unlike men, do not be- 
come infirm and decrepit with advancing years, but are rejuvenated 
with the decades they have passed. However, I will advance as a 
correct syllogism, that the Philadelphia College of Pharmacy was 
founded on broad ethical principles to supply a public need for the 
specialized and practical instruction of those entrusted with the 
protection of the public in the art of preparing drugs and com- 
pounding medicines, and that her officers and faculty have with 
honor and fidelity always adhered faithfully to the precepts and 
high ideals of the founders. To these truths we can attribute 
the success that has made her the model school for pharmaceutical 
education. 

Despite the trying experiences and the greatly added duties 
and responsibilities that have come with the great strides made 
in the sciences and in the modern methods of education, she has 
unfalteringly maintained her principles. With each precept sus- 
tained, with each difficulty mastered, with each advance carefully 
planned and faithfully executed, she has grown stronger and 
stronger and to-day her renown and her achievements for pharmacy 
are indelibly stamped upon history and every citizen of this common- 
ly eajth should be proud of her standing- and jealous of her success 



^""'M^risn Philadelphia College of Pharmacy, 239 

and future prosperity in wider fields of usefulness and research. 

Surely she has fulfilled the prediction made by that eminent 
scholar, medical teacher, and author, Dr. Geo. B. Wood, " that 
the Philadelphia College of Pharmacy would render the City of 
Philadelphia the centre of pharmaceutical education." 

The success that has attended the College is undoubtedly very 
largely due to the exemplary men who have been elected as officers. 
The presidency has always been filled by men of marked ability 
and sterling character and broad experience who have been promi- 
nent in public afifairs and assumed a full share of the duties and 
responsibilities of useful citizenship. Eight gentlemen have been 
elected as the chief executive since the founding of the College 
in 182 1. 

But I must not forget the admonitions Doth spoken and implied 
by the chairman of the committee in charge of this public function. 
First. He wanted me to limit my speech to two minutes for fear 
of tiring the audience. I crave your indulgence just a while longer 
even if I do exceed his time limit. Second. I was to refrain 
from poetical effusion. No fear of driving you away in this 
manner, the muse is sleeping, if not dead. Third. I was not to 
attempt oratorical flights. He possibly did not realise what a dead 
weight I am in this respect as I have never been accused by any 
one of being an orator. But this was not the reason he assigned. 
He intimated that the orators would follow and that the pyro- 
technical display would be the finale. Again I was not to delve 
into historical reminiscences, but I cannot refrain from straying 
from his straight and narrow injunction and reminiscencing just a 
little. 

The first president was Charles Marshall, of whom it has been 
said that few nobler men ever lived." 

The second was William Lehman, a scholarly pharmacist and 
legislator who for fifteen consecutive years was elected to the 
Pennsylvania Legislature and whose name was associated with 
many of the internal improvements of the State. 

The third was Daniel B. Smith, who served as president for 
twenty-five years. He was a happy combination of business man, 
philanthropist, literary and scientific scholar, teacher, editor, and 
author. A man remarkable for the versatility of his attainments 
and who was associated actively with most of the scientific and 
charitable organizations then existing in the city. 



240 Philadelphia College of Pharmacy. { ^""-May '"mi*'"'"' 

The fourth was Charles ElHs, who succeeded to the business 
of his preceptor, Charles Marshall, and whose name for several 
generations was well and favorably known in the wholesale drug 
business of the city. 

The fifth was Dillwyn Parrish a calm and dignified friend noted 
for his excellent judgment and wise discretion. 

The sixth was Charles Bullock another man of attainments who 
devoted a large portion of his life to the development of the Franklin 
Institute and of this College. 

The seventh was that " Grand Old Man " William Jenks whose 
conviction and love for his Alma Mater caused him to immediately 
resign the honor and duties of the office so that a younger man 
of energy and aggression might be elected. 

The eighth is our present President, Mr. Howard B. French, 
whom we are pleased to have with us on this occasion as our 
honored guest and likewise to have on dual exhibition in this life 
like reproduction, a magnificent example of the art of the artist. 

Since 1872, Mr. Howard B. French has been officially connected 
with the College as a trustee and since 1900, as our President. 
Without detracting an iota from the veneration and esteem in 
which we hold the memory of his predecessors in this office we 
can truthfully say that he combines in his personality most of the 
good qualities of all of them. 

In spite of his large commercial and financial interests, despite 
the demands of the public, he has always managed to give close 
attention to the needs of the Philadelphia College of Pharmacy. 
You who know Mr. French know that he is a most strenuous 
worker, whose determination, zeal and energy combined with his 
executive ability enables him to accomplish a vast amount of work. 
He is one of the progressive spirits who are planning, not for the 
present day and generation, but whose wise forethought will make 
the progress of future generations a possibility and conservative 
old Philadelphia a model modern city and the best of the large 
cities in the world. 

His love for the College, his devotion to her interests, his un- 
selfish and indefatigable labors in her behalf, his indomitable cour- 
age and energy, his magnetic enthusiasm, the influence of his 
practical leadership have all been potent factors in determining 
her progress and setting the pace for future advancements. 

These are but some of the traits exhibited in his official activities 



^""'May'ian*'"'" } Philadelphia College of Pharmacy. 241 

and coupled with a personality, cliaracterized by high ideals and 
virtues, have endeared our President to the members and alumni 
of the College. 

A short time ago, some of the members of the College con- 
ceived the idea that it was only proper and due that some public 
recognition should be made of the unselfish labors of our President 
for the betterment of the College; some testimony given of our 
regard, esteem and love. A meeting was held to consider the 
subject and it was decided to appoint a committee to present to 
the Alumni and members a plan to honor him and at the same 
time add to the valuable collection of portraits owned by the 
College, by presenting by popular subscription a portrait in oil 
of our president. 

The response of the Alumni was spontaneous and the committee 
have been over- joyed at the demonstrations of loyalty and the 
enthusiastic support that has accompanied the movement. An 
artist of high reputation was selected and we have before us now 
his finished commission, the excellent and almost speaking likeness 
of our honored president. 

I esteem it as a great honor to act as the representative of the 
more than 1200 contributors to this fund, and in their behalf present 
to the College this portrait. In their behalf, I ask that it be 
accepted as a slight tribute to the efforts and personal worth of 
the original, a token of the regard and esteem and love that the 
Alumni has for our president. Further, this occasion signifies and 
this gift symbolizes the loyalty of our Alumni who are jealous 
of the fame and honor of their Alma Mater. An aggressive Alumni 
who are fully alive to her interests and who are praying that a 
better location and more ample facilities may soon be at her com- 
mand, and with enlarged opportunities still greater achievements 
are confidently promised. 

We ask that this portrait be preserved and safeguarded and 
trust that it may be but another inspiration to the members for 
the perpetuation of that integrity, sincerity, fidelity and adherence 
to principles that have always characterized the management of 
the institution. May the sentiments promulgated with its inception 
and associated with this movement live for ever. May the portrait 
as it hangs on the College walls prove a silent, yet effective example 
worthy of emulation, that shall stimulate the coming generations 
of students to their highest attainments and maintain the Phila- 



242 Philadelphia College of Pharmacy. {"^'"-May'ign*™' 

delphia College of Pharmacy in the lead of all pharmaceutical 
education. 

The portrait was accepted on behalf of the College by Richard 
V. Mattison, M.D., First Vice-President of the College. 

address of acceptance of portrait, by dr. mattison. 

Honored President, Mr. Toastm aster. Fellow Alumni and 
Friends : 

By virtue of my position as First Vice-President of our Col- 
lege, I am accorded the rare opportunity of accepting upon behalf 
of our members, this portrait of our friend and fellow-alumnus, 
Mr. Howard B. French, a memento in perpetuity of the love 
which the associates of our self-denying president have for his ever 
charming personality. 

To voice this affection and high esteem, in which more than 
twelve hundred of our alumni have joined, is, I take it, the real 
object of this assemblage gathered to-night about this festive board. 
But in voicing it what can I say that you do not already know about 
this man whose thoughtful, clear-sighted, far-reaching and most 
unusual labor upon behalf of the Philadelphia College of Pharmacy 
has been and is of such transcendent magnitude that we even now 
scarcely appreciate the enormous possibilities which have been 
opened up to us through the untiring devotion of our president 
to our college interests. 

As we, therefore, as his fellow Alumni, unite to do him glorious 
honor this evening, let us accord him with most joyous acclaim 
the fulsome praise which his deeds command and, in heartsome 
tribute to the rugged, manly personality of Mr. Howard B. French, 
unite with the immortal bard in Hamlet and, but slightly para- 
phrasing, say, " Here is a man that, take him all in all, we shall 
not look upon his like again " — our President. 

response by president FRENCH. 

Mr. Toastmaster and Gentlemen: 

My physician positively forbade me saying one word. You 
have been exceedingly kind. You have honored me beyond, far 
beyond, my desserts ; and I thank you all for having me here with 
you to-night and for doing honor to the College. 



^""'MayrwiL™'} Philadelphia College of Pharmacy. 243 

THE ADDRESS OF HON. JOHN E. REYBURN, MAYOR OF PHILADELPHIA. 

The address of Mayor Reyburn was in the nature of a tribute 
to President French's services " as a citizen whose pubHc spirit and 
unselfish labors have been of the greatest value in his relations to 
this community." 

He said: No man other than he could stand before a Philadel- 
phia audience to-day and claim with less dissent or with more 
truth that he has performed his whole duty toward this city. He 
has given up not simply honors, but even days to studious thought 
and active participation for the advancement of the public welfare. 
His services were not perfunctory, but enlisted the generous im- 
pulses of his nature; and he gave actively the very best thought 
and the most strenuous effort for the good of Philadelphia. I 
stand here to-night to acknowledge before this assemblage the 
obligations I am under personally to Mr. French for his strong 
common sense and for that equipoise of character which made 
his counsel and co-operation so valuable. There was with him a 
sort of holding things level, as you know a square man always 
does ; and you can tell instinctively when a man is square. He has 
that conservative characteristic which I might call a holding back ; 
and yet there was a strength and a fervor in his holding back. It 
was a powerful influence in itself ; and I always recognized him as 
a safe guide and a reliable counsellor." 

His Honor, the Mayor, further said : To be the head of a 
great school like that of the Philadelphia College of Pharmacy, 
which for ninety years has proven its worth in our community, is 
in itself an honor of which any man might be proud. It is really 
a great distinction. We know how Mr. French has carried on 
the work of this institution — not carried it on in the sense of 
supporting it with money or with great gifts and all that, but by 
his personal, every day interests in its management, in the welfare 
of its students and in all that springs from an institution of this 
kind and that makes it efficient and a benefit to the community in 
which it is located. As its head, its director and its guide, he has 
kept the College in the exalted position which it occupies to-day 
and has occupied in all the years of its useful existence. There 
can be no question that it is to have a more extended sphere of 
activity. Indeed, in the logic of events, it cannot fail to share 



244 Philadelphia College of Pharmacy. {^'"•Maj^m"'"' 

in the great development that is sure to come to our coninmnity 
and to the whole world in the next generation. Its mission will 
be ever onward and upward. 

" Now this institution deserves to be and ultimately will be 
placed in a location commensurate with its merit and importance. 
The example it has furnished, the influence it has wielded, and the 
great things it has accomplished for the good of humanity, not only 
in the city and State but in the United States, and I might say, 
throughout the whole world, entitle it to proper recognition, with 
the men who have been connected with it, the College has stood out 
among these institutions of learning, of art and of science, which 
have made Philadelphia famous." 

Continuing, the Mayor said : " As I have said, we want to see 
the Philadelphia College of Pharmacy where it should be — \\c 
might as well say it frankly — upon the Parkway. And if there 
is anything that I can do to aid in placing it there it will be done. 
The College should be in a commanding place, where it may be 
seen by everybody, that the world may know of the good it is 
doing and will do." 

ADDRESS BY NATHAN C. SCHAEFFER, PH.D., LL.D., STATE 
SUPERINTENDENT OF PUBLIC INSTRUCTION. 

Dr. Schaeffer, among other things, said : 
When I was a boy, studying history, I noticed that there 
were certain names on the pages of that history that had the 
surname ' great ' attached to them ; and I asked myself ' What 
is it that makes the man great ? ' I noticed that there were only 
two classes of men in history to whom that surname ' great ' was 
given ; the one class being composed of men who had been eminent 
in the State ; men like Charles the Great, Frederick the Great, and 
Alexander the Great. There was another class of men surnamed 
' great ' who had been eminent in the church, men like Leo the 
Great and Gregory the Great. And my perplexity grew when I 
asked, ' Why is it that men in past ages have only achieved great- 
ness in two lines of human activity, the Church and the State." 
Well, in my boyish eyes the greatest man in the community was 
the one who could draw the biggest check and have it honored 
at the bank ; but I very soon discovered that wealth does not 
make men great on the pages of history. You never read of 
Rothschilds who were great. Away back in the days when Virgil 



"^""'May'i^^n^™'} Philadelphia College of Pharmacy. 245 

wrote and CicerO' spoke there were men so rich that they dissolved 
pearls in goblets of wine to make the drink more costly. But 
if your life depended upon it, I venture to say, not one of you 
could mention a single one of those rich men's names. In spite of 
their wealth their memories have been buried in oblivion. Wealth 
does not make men great. A man may be a manufacturer and 
pile up profits so that they will fill the vaults of a bank, but that 
does not make a man great. I got the notion that it was scholar- 
ship that made men great, for I found that on Commencement Day 
prizes and honors were awarded on the basis of scholarships. But 
when I began to study the life of Frederick the Great I found in 
it nothing of scholarship to boast of. He never learned to read 
his native German with any sort of fluency. Voltaire used to say, 
in the morning, ' Now I must go and wash the King's dirty linen,' 
meaning thereby that he must go and correct the King's French. 
Frederick never could read French accurately, and yet he was 
great. Scholarship never makes a man great. A man may be 
the President of a College, and noted for his scholarship, and yet 
never achieve greatness. 

Is it political position? Well, many men have held political 
positions and they have sunk into oblivion. It is not political 
position either that helps to give a man his place amongst his 
fellowmen. Schleiermacher, in his essay on Frederick the Great, 
says ' that men are great in the degree and to the extent that they 
exert a moulding influence over their fellow men and render to 
them helpful service.' In past ages the Church and the State were 
the only channels through which the sons of genius could reach 
the masses of their fellow men and thus leave their own age and 
their own people better than they found them. But the nineteenth 
century opened up a new channel through which a man can reach 
his fellow men, and that channel is the school. 

The man whom we admire and whom we have gathered to- 
night to honor has impressed himself upon the community through 
the school to whose board of trustees he has belonged for many 
years and at the head of which he has stood during a number 
of years. This Philadelphia College of Pharmacy has made itself 
felt not only in Pennsylvania, but even in the far-off countries 
of Asia and of other lands ; an(l probably it has done more for 
liumanity than some of us are able to perceive. 

In the days of John Calvin of Geneva the average length of 



246 Philadelphia College of Pharmacy. {^'" May'-i.m*'"'"" 

life was twenty-one years. To-day, in some of the States of this 
Union, the average length of life is more than forty years. Is not 
that partly due to the fact that the druggist has learned how to 
compound prescriptions for people who are sick, how to administer 
medicine so that his drugs may not be harmful but their use may 
redound to the health and the welfare of the people ? 

No one can deny that our colleges of pharmacy have done 
very much to add to human longevity. For that reason a college 
like the Philadelphia College of Pharmacy, which, if my educational 
history is all right, was not only a pioneer, but the first institution 
of its kind on the face of the earth, deserves an amount of recog- 
nition, in the history of education, that cannot be accorded to an 
ordinary school. Is it not a pioneer, is it not a forerunner, is it 
not the parent of a great many schools that are now efficient 
agencies in curing disease and in lengthening human life? 

Max Mueller says that every public man leads three lives 
while but one life is seen by the people at large. That is the man's 
public life. Another life is seen only by the man's intimates, by his 
wife and by those who live with him under the same roof. That 
is the man's private life. I have always felt that a man deserves 
great praise when his private life is in strict accord with his public 
life. And it is for that reason that we are constrained to praise 
the President of the Philadelphia College of Pharmacy. What 
is the third life that every man in public life leads? The third life 
is the inner life, visible only to the man himself and to his Maker 
on high. When a man's inner life corresponds with his private 
life and his public life, then we have a model man; the private 
life and the public life of the man being but an expression of 
that inner life which is visible only to the man himself and to 
his Maker. From all that I have been able to learn of the gentle- 
man whose picture is before us, these three types of life have been 
in harmony throughout his long career. 

Now, one word more and I am done. I have had my dreams ; 
and when I visited the College of Pharmacy and saw how every 
inch of space had been utilized I could not help wishing for that 
contemplated boulevard with plenty of ground and the requisite 
facilities to accommodate this institution. Philadelphia is the centre 
of medical, dental and pharmaceutical education. When I was in 
the Berlin University, if a man was a Philadelphia dentist he had 
plenty of practice. Our University here draws a hundred more 



^""May^gn*™ } Philadelphia College of Pharmacy, 247 

students from foreign countries than Yale or Harvard or any 
university on the Atlantic Coast. This College of Pharmacy 
draws students from Asia and other foreign lands. It is re- 
nowned, both at home and abroad, for the thorough education 
which it gives. And my wish to-night is that the College of 
Pharmacy may grow and flourish and that its present President 
may live long to carry out the plans for its prosperity that he is 
cherishing. It is also my wish that the official life of our Mayor 
may be prolonged so that that Beautiful Philadelphia " shall come 
when these gray heads can see it and that when that Philadelphia 
Beautiful " shall be realized one of the ornaments to which the 
visitor may point with pride will be the new building, on the 
Boulevard, of the Philadelphia College of Pharmacy. 

ADDRESS BY EDWARD JAMES CATTELL, ESQ., OF THE BUREAU OF 
STATISTICS OF PHILADELPHIA. 

Mr. Cattell, who was introduced by the Toastmaster " as the 
silver-tongued orator of Philadelphia " made an address which 
alternated with flashes of humor and eloquence. He said in part : 

It seems to me, gentlemen of Philadelphia, that the occasion 
of the presentation of this portrait, the fact that we are here honor- 
ing this gentleman who stands for a type of man good to the core 
because he wants to be good, not because he has no opportunity 
to do evil, testifies the highest type of public spirit and is full of 
promise for the city we all love. 

Now, to speak the whole truth — I love Mr. French. T have 
known him these many, many years. And as I looked upon him 
to-night, there came back to me an old memory of fifty years ago 
when, early in the morning of a day in Spring, I first caught sight 
of his beautiful home in New Jersey. It was a building of snowy 
whiteness, with strong and beautiful lines rising with a dignity 
all its own, out of a grove of trees. Something about it was 
typical of that purity of life which the American home stands 
for everywhere. As I looked at Mr. French to-night, under his 
crown of silver, — God-given token of duty well done, — it seemed 
to me that: in his character, in his life record, in all that he 
has done for this city that I love, I could see the same strong, clean 
lines, the same untarnished purity, that stood out so gloriously 
in the morning sunlight when T first beheld the dear old home 
in which he learned from mother and father those noble principles 



248 Philadelphia Colic i^c of Pharmacy. { ^^Mar'iiii*'""' 

and generous impulses which have always distinguished him. 1 
have at home a bank check drawn by his father — one of the finest 
men I ever met — to my father, sixty-five years ago. Our parents 
respected and trusted each other. I respect and love your Presi- 
dent and am proud to tender this tribute to his worth and give this 
public recognition of what he has done for this city. 

remarks by hon. isaac johnson, state board of charities of 

pennsylvania. 

Mr. Toastmaster and Friends of Howard B. French : 

Surely no request from Mr. French to myself to say a word on 
an occasion like this could be denied, even though I only expressed 
my honor of being called upon. I thank you for the compliment 
you have paid this man here to-night. I have known Mr. French 
a number of years in connection with the State Board of Public 
Charities. What you have said about him to-night as he is 
known in the ordinary walks and avenues of life meets a warm 
response in the heart of every man who has met him in this great 
work. We do not meet often enough to speak to each other, during 
our lives, of the work in which we are engaged ; as a rule we wait 
until our co-workers are dead, and then we build monuments to 
their memory when these cannot do them any good. 

It was a great pleasure for me to come to-night to this dinner, 
to be present at the presentation of this portrait to the School 
of Pharmacy and to hear the kind words spoken of this man 
and to himi when he can hear them and appreciate them. It is 
a very great pleasure to be told by those who have known him 
longest and best that, as he has travelled upon this stream of 
life until now getting into the way of being called an old man, 
he has never thrown any mud, was never indiscreet and that 
he has lived in a city that is cleaner and better for his living in 
it. What compliment can be paid a man equal to this? The 
distinguished educator who spoke here to-night pictured tO' us 
the wealthy and the educated ; and he has told us that it is not 
wealth or education that makes men great. No ; it is a man who 
picks a fellow up from the roadside and helps him over the rough 
places of life ; it is a man who goes through life, strewing it with 
blessings — he is the great man. And onl/ he will history perpetuate 
the memory of, 



^'°May'"i9n!'""} Philadelphia College of Pharmacy. 249 

ADJOURNMENT. 

The ceremonies closed at 11.20 p.m. with a round of cheers for 
President French, in which the entire company, under the lead 
of the Toastmaster, joined with great enthusiasm. 

NAMES OF SUBSCRIBERS TO PRESIDENT FRENCH 
PORTRAIT FUND. 

The collection of the subscriptions was placed in the hands of a 
special sub-committee, of which Mr. C. Mahlon Kline was the 
chairman. The replies received, with the subscriptions, showed 
not only the high esteem which the alumni have for President French 
and their appreciation of his devotion to the college, but uniformly 
expressed the affection of the alumni for the college and their desire 
to assist in every way in advancing her interests and in aiding her 
in retaining the leadership she now holds. 

One of the most pleasing letters received as showing the loyalty 
of the alumni was that from the widow of a deceased alumnus^ who 
in sending her contribution in memory of her husband added, " it 
would please him to know that I could help his Alma Mater in so 
small a way." As the chairman of the Finance Committee has said, 
" the generous responses of so many of the alumni show that they 
have the welfare of the college at heart, and these sentiments are 
really more important to the institution than the donations them- 
selves." It was soon apparent after the Committee got to work 
that this movement to honor President French had become a move- 
ment for welding the alumni together into a coherent and efficient 
organization and was indeed stimulating not only to the members 
of the Committee but to all those engaged in the college work. 

The following is a list of names of the members of the College 
and alumni who subscribed to the President French Portrait Fund, 
the total number being something- over one thousand : 

Gus G. Anderson, S. D. Addis, F. J. Althouse, Joseph C. 
Andrews, F. C .Albright, W. E. Allen, H. P. Arnold, John Ayres, 
H. V. Arny, Robt. B. Anawalt, Robt. W. Allen, Louis K. Acker, 
Frank I. Adams, E. F. Allen, J. K. Auginbaugh, William Appmann, 
M. D. Allen, Franklin M. Apple, WilHam H. Andrews, Milton S. 
Apple, Howard Albert, James D. Adams, James A. Allen, Charles 
Franklin Adams, William C. Aughenbaugh, Paul Anspach. 

Russel T. Blackwood, George B. Beakey, John D. Burg, Maxwell 



250 Philadelphia College of Pharmacy. ]'^" Ma"% i9n*""* 

M. Becker, George Blinkhorn, Grace Lu Babb-Abbott, Charles H. 
Baldwin, Warren B. Beckler, J. S. Beetem, J. O. Burge, Howard H. 
Boltz, S. A. E. Brallier, Thomas L. Buckman Charles A. Bye, 
Isaac A. Braddock, James Stanley Breen, Peter Bienkouski, Helen 
R. Burns, R. H. Brennecke, S. J. Bannan, John J. Bridgeman C. W. 
Baas, Russell G. Bush, George H. Borrowes, John H. Booth, Jacob 
M. Baer, Henry C. Blair, George M. Beringer, Howard J. Baer, 
Irwin A. Becker, Chas. M. Butcher, Mitchell Bernstein, Chas. J. 
Biddle, Fred W. Branin, W. C. Bauer, Geo. M. Beringer, Jr., W. E. 
Brown, H. A. Burkhart, D. A. Buehler, Jesse N. Blalock, C. H. 
Bernhard, Chas. H. Butters, Henry Blithe, Lulu Brookes, Virginia 
Brookes, Oliver G. Billings, B. Henry Balle, Albert E. Brown, Willis 
E. Bowen, Alexander Bachmann, W. C. Burchfield, Chas. B. Baum- 
gartner, H. O. Baer, Samuel Bartholomew, S. J. Banman, Wm. H. 
S. Bateman, Jennie Block, Wesley J. Barrett, Edwin M. Boring, 
Ray P. Brown, Edw. H. Buehler, Fred J. Benner, E. H. Burhl, C. L. 
Bonta, Chas. W. Baas, Edgar Breneiser, E. P. Barr, M'. W. Britcher, 
Geo. Bille, Elam Brubaker, E. F. C. Beecham, J. W. Beckwith, 
James Buckman, Robert W. Beck, John P. Bates, Max Barkel, 
T. H. Boysen, F. A. Butter, W. A. Bright, F. A. Bunting, W. L. 
Bucher, J. C. Boyer. 

E. O. Criswell, Albert Cliffe, L. Corson, J. C. Coscey, Wm. F. 
Cramer, Jr., P. V. Cooper, C. C. Church, Nathan A. Cozens, Edward 

B. Clark, Wm. E. Cassell, F. F. Coleman, Katherine Cliffe, Norman 
H. Cloud, R. B. Claudy, M. Costello, W. G. Culby, C. F. Carter, 
A. D. Constock, Virgil Coblentz, Theo. Campbell, E. F. Cook, David 
Costelo, Albert R. Calhoun, Milton Campbell, F. W. Culler, F. H. 
Cappeau, Geo. J. Coleman, Roy T. Cope, J. W. Cotterel, A. T. 
Clayton, Clarence H. Campbell, W. A. Clingan, S. Ross Campbell, 
Geo. H. Colton, Thos. C. Coltman, W. A. Carpenter, J. W. Crumbie, 

C. R. Carrington, T. F. Crawford, H. V. Crawford, W. R. Calvine, 
A. D. Cuskaden, H. C. Clapham, H. G. Carter, W. L. Cliffe, H. M. 
Carey, Geo. L. Carman, John E. Carter, Clarence Croft, Jos. Carey, 

G. J. Crumbis, L. B. Curtis, A. B. Clark, G. F. Crouse, Chas. S. 
Closson, Lane V. Collins, H. L. Cox, F. W. Cotton, L. B. Coley, 
John H. Collins, Amanda M. Carslake, Clarence H. Corp, J. K. 
Challenger, E. D. Chipman, Louis G. Clarke, E. D. Crouse. 

H. B. Dilatush, H. J. Darr, Robert L. Dubbs, Walter C. Dugan, 
L. H. Dielman, R. G. Dunwody, P. R. Donmoyer, W. A. Dorman, 

H, M. Dorman, W. H. DeBeust, S- B-, Pgivis, L. A. Dresbach, J. H. 



^""Mayrim™') Philadelphia College of Pharmacy. 251 

Dewees, Kate M. Davidowitch, Henry H. Dancy, Oscar C. Draper, 

A. Dougherty, J. H. Dewees, Norman R. Dean, Geo. J. Durbin, 
H. D. Dietrich, C. G. Dodson, Chas. F. Dare, Wm. T. Douglass, H. L. 
DeKalb, Louis Dielman, John H. Dawson, W. E. Dittmeyer, Guy S. 
Dunbar, C. A. Duncan, WilHam DuHn, Geo. B. Davis, Harmon 
Dilks, Jr., Chas. B. Dierolf, W. R. Dawes, Alex. Dubell, C. Wilfred 
Dare, Howard S. Davis, T. I. Deibert, Servill Douglass, Wm. B. 
Davis, Edwin A. Donecker, Thos. Donaldson, H. H. Dealeyne, 
W. R. Decker, Philip C. Dosch, A. J. Ditman, T. S. Deen, John T. 
Doughty, Chas. W. Dirmitt, C. W. Dare, G. C. Davy, Jos. T. 
Dougherty, R. B. Dickinson, C. Lewis Diehl, Wm. Drett. 

C. P. Eves, Jos. W. Ehman, J. Evans Eckman, Edw. A. Eyer, 
Chas. W. Eckenroth, J. W. England, Geo. B. Evans, E. G. Eberle, 

B. H. Eichold, Samuel Evans, Henry Eberhart, H. S. Eckels, T. B. 
Eisenhart, Evan T. Ellis, D. F. Eft, Horace W. Estlack, M. Bruce 
Edwards, J. S. D. Eisenhower, Chas. L. Eberle, Wm. Evans, Abner 
T. Evans, Chas. W. Evans, S. C. Ensminger, Maurice H. Eby, 
James M. Ebert, Clarence H. Eldon, E. G. Eberhardt, Mrs. Jose- 
phine English. 

James A. Ferguson, W. O. Frailey, Jr., Frank B. Fleming, C. 
Falkenhainer, Geo. D. Feidt, Harry Fritsch, Ralph A. Forrest, Carl 
D. S. Fruh, Gustav A. Fruh, Dunning French, Samuel H. French, 
Jr., Lawson C. Funk, Benj. F. and Saml. W. Fairchild, C. Stanley 
French, J. R. Fulton, John P. Failing, H. B. Foresman, J. C. Falk, 

A. S. French, Clarence R. Fox, Peter P. Fox, B. L. Fuser, Martin E. 
Farrell, R. W. Fisher, F. D. Ferrell, Richard L. Fishbirne, Nelson 
Fry, Warren W. Flitcraft, Wm. O. Frailey, Henry Fisher, C. M. 
Forney, Pliny Fishburne, T. A. Fessler, Lee James Farley, Geo. 
Castor Faunce, C. F. G. Feterolf, Adolph Fischer, Rolland H. 
French, Jesse A. Fowler, Susan E. Ferguson, J. M. Fackenthall, 
Andrew G. Frey, E. H. Fienhold, Oscar C. Fletcher, Robert S. 
French, Harry B. Fasig, F. W. Fluck. 

E. R. Gatchell, P. N. Guise, W. H. H. Githen, J. P. Garvey, 
Philip Goll, D. C. Gibboney, Ray D. Gilliland, O. H. Gentry, Jr., 
Charles W. Greenough, L. Goldsmith, George L. Genz, John A. 
Govry, George A. Gorgas, J. M. Good, Harold D. Guenther, Wilbur 

B. Goodyear, W. H. Gano, O. E. Gessford, Frank Glei n, Edward Z. 
Gross, E. B. Goico, Charles T. George, John K. Garland, S. Horace 
Gotwalt, W. H. Guest, A. C. C. Gamer, H. C. Grim, Norbert H. 
Grove, J. Clarkson Griffith, Walter J. Garver, Myatt E. Goring, 



252 



Philadelphia College of Pharmacy. 



I Am. Jour. Pharm. 
■( May, 1911. 



F. Gutekunst, Amos C. Glise, E. H. Gingrich, J. F. Gyming, Francis 
Green, James A. Garvey, Hyman Greenberg, G. W. Goldsmith, P. E. 
Grunder, John D. Groves, C. P. Greter, Edmund R. Gatchell, H. 
Guest, Willard Graham, WilHam P. Graybill, E. W. Garber, Fred. 
Griesemer, John Goldbach. 

James J. Hodil, Frank H. Holzschuh, Lorne E. Hastings, Curtis A. 
Harbold, Luther S. Henkel, Frank G. Hastenan, WilHam T. Hankey, 
*M. Hall, George W. Hackenberger, D. H. Holcombe, Harry R. 
Hess, Alfred Heineberg, William Hieckie, Bruce C. Hallowell, D. H. 
Hage, John F. Hancock, Charles R. Haig, H. L. Heim, Joseph A. 
Heintzelman, C. P. Hendrickson, Eugene M. Holroyd, T. A. 
Hohmann, Lewis C. Hopp, Hance Brothers & White, J. O. Howells, 
WilHam Hiecke, Charles W. Hansen, Mrs. Carrie E. Howard, John 
H. Holcombe, John H. Hahn, Ernest W. Hermann, Ambrose Huns- 
berger, Howard J. Houk, Harry C. Hughes, F. H. Harmening, 
John F. Hancock, Aquila Hoch, Wihiam J. Heim, H. H. Haak, 
J. J. Haley, Christian Heim, Henry W. Harper, Susannah G. 
Haydoch, Mrs. W. H. Hand, J. E. F. Hicks, W. Clyde Harris, 
Norman E. Hertzler, Fred C. Heverly, Elmer Heinze, Emile Hey- 
dureich, G. G. Hubber, E. C. Hathaway, Harry L. Hetrick, E. F. 
HoweH, J. N. C. Hetherington, G. W. J. Hoffman, D. H. Hilms, 
T. E. Hickman, W. O. Higgate, H. G. Harnig, A. R. Hesske, James 
S. Holt, B. Russell Hurst, Ruben G. H. Hayer, Adam B. Heckerman, 
W. Smith Heiges, F. E. Himmelwright, Frank D. Hall, Oliver B. J. 
Haines, J. O. Harrison, Warren E. Hunt, Chas. N. Harr, Robt. A. 
Hatcher, W. H. Hostelley & Co., Harvey Harding, Chas. J. Harvey, 
H. L. Horst, Chas. S. Herron, Gustav Hahn. 
Howard E. Ingling, S. M. Irvin. 

Wm. A. Johnson, Calvin Jordan, E. F. Johnson, R. E. Jones, 
Howard M. Jordan, Jos. Jacobs, L. M. Jones, C. N. Johnson, A. B. 
Johnson, Eugene J. Jacobs, Henry A. Jorden, Edw. B. Jones, Hilbert 
P. John, C. N. Jacoby, Wm. C. Jones, Wm. C. Jaeger, Wm. F. 
Jungkunz, Benj. H. Jenkins, EHsha Roy Jones, Walter H. Joerg, 
L A. Jennings. 

Oscar P. Kraemer, Geo. C. Keen, H. L. Keipel, Geo. H. Kille, 
W. A. Kulp, Frank B. Kirby, Frank Kline, S. R. Ketcham, Ray W. 
Kottka, R. K. Kincaid, Frank G. Kerr, Solomon Kleckner, Edgar T. 
Knoop, C. H. Krauter, W. H. Kunkle, H. L. Klopp, E. L. Klopp, 
Henry Kraemer, Otto Kraus, D. M. Knabb, H. A. Kalboch, J. Frank 
Kilgus, Franklin Kern, E. M. Korb, Geo. H. Kramer, Augustus H. 
Keller, A. H. Keller, Robert A. Koempel, W. A. Kulp, R. Kindig, 



^°'Ma7i9?r''"} Philadelphia College of Pharmacy. 253 

G. H. Knowlton, Wallace E. Klopp, Otto F. Koehler, Christopher 
Koch, E. F. Kessler, H. G. Kambach, D. Geo. Kocher, Edwin H. 
Kercker, Alex. G. Keller, John Kentworthy, Benj. Krehl, Jacob L. 
Kolp, J. F. Kiedaisch, Jr., W. M. Kilgus, Thos. J. Kelly, Carl Krebs, 
Jas. B. Keener, Harry C. Karns, E. L. Klopp. 

Fred G. Luebert, David C. Lyman, Wm. J. Laros, C. W. Ludwig, 
O. Luther Latchford, Wilbur L. Lafean, Eugene Lamparter, J. 
Grier Long, Ivan Lichtenstein, P. C. M. Laughlin, Miss Helen 
Loughlin, A. G. Luebert, E. H. Lauer, Jos. L. Lemberger, Wm. E. 
Lee, Clement B. Lowe, J. K. Lilly, Chas. H. LaWall, Harry A. 
Laesck, Chas. Leedom, Robt. C. Lippincott, Thos. D. Laws, Miss 
Levien, G. T. Lehman, A. B. Levi, A. E. Lounds, S. W. Lehman, 
Fred. O. Luhr, Harry A. Lloyd, William Laval, William Lamar, 
C. S. Long, Charles Lehmann, John F. Loehler, A. W. LeVan, Geo. 
T. Lambert, B. S. Lancaster, Mandell Light, Howard M. Levering, 
S. W. Leidich, Richard Lackey, H. J. Lackenmayer, E. J. LaWall, 
Henry T. Lefferts, Chas. T. Lankins, Harry W. Leamer, E. C. 
Lafean, A. M. Leine, Geo. B. Levan, Wilbur J. Leib, Jas. R. Lorah, 
Wm. H. Lantz, Chas. Foster Lilly, T. Ladakis. 

Wm. D. Maun, Jno. Moffet, E. S. Mohn, J. E. Mohn, C. F. 
Moeller, A. G. Miller, C. A. Mueller, Thos. F. McCoy, E. Spencer 
Moser, J. C. Mayers, W. B. Means, Raymond W. McCarty, Mrs. 
J. H. Miller, Geo. F. Maddock, R. S. Marshall, Paul L. McConomy, 
Homer P. Middlekauff, Frederick Wm. Meink, J. W. Mader, C. E. 
Mengel, John A. McFall, Wm. N. Martinell, Geo. F. Metzger, L. J. 
Milk, D. A. McMillen, Edwin R. Mohler, C. H. McLaughlin, Wm. 
Mclntyre, Harry Matusow, Frank E. Morgan, Adolph W. Miller, 
Caswell A. Mayo, Frank X. Moerk, Richard V. Mattison, Robert 
McNeil, W. Clement Mutty, Clayton E. Morgan, Max Morris, C. H. 
Meredith, Thos. N. Millikin, Wm. S. Maltman, Chas. M. Morell, 
Wm. H. Meek, E. O. Moyer, Geo. A. Moleen, Howard O. Markle, 
L. Cleveland Martin, Clayton R. Myers, Oliver B. McClements, 
Harry E. Mickey, Lloyd L. Mountain, C. Menkmeller, P. L. More- 
head, John A. Martin, Wm. Mittlebach, Chas. N. MeClure, John A. 
McGonigal, Burt,E. Moritz, L. A. Meyers, Chas. Maier, Mrs. L. 
Mandebaum, Chas. B. McLaughlin, Lewis N. Moyer, Geo. F. 
Maddock, Geo. C. Mackey, Hanford B. McGehee, Robert B. Matter, 
Charles Mann, J. Harvey Miller, Jos. F. McDonnell, Bertha Mueller, 
Conrad G. Moell, L. J. Meyers, Thos. D. McElhenie, Clem. B. 
McCullough, Alfred Mellor, Henry J. Myers, S. Mason McCollin, 
John C. Montgomery, C. Carroll Meyer, L L. MacPherran, J. C. 



254 Philadelphia College of Pharmacy. } ^'^May^m""* 

McVicker, John F. McGovern, Henry Mittlebach, Jos. McKee, 
Wm. A. Markley, John J. Macphee, Robert W. Madeira, B. M. 
Magill, C. M. Miller, T. W. Meissner, Jr., C. M. McClure, Frank J. 
Maier, Garfield March, C. B. Miller, John D. Moore, H. McDavit, 
John Maier, W. M. Miller, I. C. Marquardt, J. H. McCracken. 

S. S. Newcomer, Thos. O. Nock, Henry A. Newbold, Edwin L. 
Newcomb, Kissag M. Nahikian, W. H. Nelson, Augustus H. Nolte, 
L. A. Neiman, Sarah L. Naley, Wm. G. Nebig, E. Geo. Nickum, 
Geo. A. Newman, O. C. Neumeister. 

Harry W. Ohming, Milton M. Osman, Melmoth M. Osborne, 
O. W. Osterlund, Rudolph H. Ouering, O. M. Oleson, C. Herman 
Oberholtzer, Walter H. Orrick. 

Gustavus Pile, Jos. L. Pennock, H. J. Pierce, J. S. Picking, Jr., 
David G. Potts, Jos. A. Palen, J. M. Pasold, H. R. Palmer, J. L. 
Patterson, David DeSilva Pereira, Theodore Pachali, Henry Plenge, 
Adam W. Pflieger, Wm. R. Powell, A. B. Petrie, Samuel R. Pearce, 
Powers, Weightman, Rosengarten Co., Adam Phromm & Co., T. B. 
Power, Mrs. Bertha 1. DeG. Peacock, E. S. Perrenot, Wallace 
Procter, Warren H. Poley, J. C. Peacock, E. M. Piatt, Chas. W. 
Pepper, M. Gertrude Powell, Samuel E. Phorley, T. H. Potts, W. A. 
Pierce, Geo. L. Pfeiffer, Arthur Peiffer, Geo. L. Paullin, J. Heber 
Parker, Samuel A. Pearson, Adison A. Piatt, John F. Patton, W. 
Procter, Jr., D. G. Potts, F. H. Parker, Edw. S. Power, D. E. Prall, 
Fred. A. Pfeiffer, R. D. Peters, E. D. Paxon, A. A. Polhner. 

J. V. Quick, Vincent DeP. Quinn. 

Percy R. Russell, Arthur D. Reagan, Eugene M. Rohrbaugh, 
Jacob H. Rehfuss, Luther K. Rhoads, John Bernard Raser, Harry F. 
Ruhl, H. T. Richards, H. O. Reinnoldt, Edw. M. Richman, J. Percy 
Remington, A. Eugene De Reeves, Geo. F. Roehrig, Edw. S. Rose, 
Wm. H. Reeser, E. P. Raab, Zebulon H. Rodes, Geo. R. Ross, 
W. C. Rogers, S. M. Reich, E. W. Raines, Frank G. Ryan, Jos. P. 
Remington, Walter A. Rumsey, A. R. Reburn, Chas. R. Rhodes, 
Herbert L. Richards, J. Lester Ranson, J. P. Rothermel, Chas. E. 
Rowe, Elmer A. Reidenbach, J. Herman Rabenau, Geo. R. Ross, 
W. H. Reed, A. N. Richardson, John Rigg, D. H. Ross, Samuel 
Rosenberg, W. E. Ridenour, Wm. G. Roof, Harry F. Ruhl, Geo. W. 
Rhodes, Ernest Rieben, W. H. Riker, John B. Reynolds, F. P. 
Riedenaner, D. J. Reese, Alfred W. Reeve, Walter E. Ruch, Chas. 
Haines Roberts, Howard Reed, Chas. Rehfuss, David W. Ramsaur, 
James S. Robinson, Jno. J. Reynolds, Leon S. Risley, Louis A. 
Rectenwald, L S. Reice, Geo. W. Roland, Warren B. Rush. 



"^"May'mL™"} Philadelphia College of Pharmacy. 255 

C. A. Seubert, Harry D. Schell, P. S. Stout, Albert H. Smith, 
H. J. Sunday, Wm. R. Shearer, A. B. Schminky, Andrew E. 
Spalding, Laura M. Smiley, Jos. A. Shrom, Geo. W. Shoemaker, 
Henry J. Schmidt, Edw. T. N. Stein, Edgar R. Sparks, Samuel 
Simes, Leir Scott, Edw. C. Stout, Geo. B. Spath, M. P. Snyder, 
E. B. Stone, Chas. C. Sniteman, Frank P. Semmel, Jr., Wm. Schleif, 
Chas. F. Shelton, Miss Rose Slobodkin, C. J. Schneider, R. C. 
Strode, Frank B. Smith, Chas. A. Scott, A. H. Stacks, W. L. Swartz, 
R. G. Shoults, H. S. Smedley, Howard A. Stonesifer, John A. Seitz, 
M. F. Schaak, L. J. Steltzer, R. C. Sharadin, A. J. Strathie, H. C. 
Swartley, Smith, Kline & French Co., Richard M. Shoemaker, 
Walter V. Smith, Samuel P. Sadtler, F. P. Stroup, Shoemaker & 
Busch, Geo. R. W. Schuster, A. J. Schlaepfer, W. A. Sickel, Jacob 
Sutliff, H. W. Scott, L. B. Switzer, Geo. Lewis Smith, J. D. Seiber- 
ling, John Geary Stroud, A. H. Schmitt, Louis N. Sahm, Herman C. 
Siegle, J. Wesley Steele, A. Milton Shiffer, F. P. Streeper, Geo. 
Strickler, Paul Smith, J. B. Schuster, A. A. G. Starck, Allen Shoe- 
maker, W. A. Sprenger, S. Arthur Shiffer, Chas. A. Schloer, James 
H. Sheridan, Horace M. Schabacker, Robert S. Sherwin, Wm. F. 
Steever, H. DeForrest Stevens, Geo. A. Siegrist, Jacob Strickler, 
Franklin P. Shaak, Emil Schaible, H. J. Schulte, Herbert E. Strauss, 
Wm. W. Sharp, Leslie W. Schwab, Harry D. Schell, Oliver Stout, 
Geo. M. Saul, Nellie J. Stevenson, S. S. Stewart, Otto W. Schmidt, 
Selma L. Schmidt, H. L. Stiles, R. A. Stofflet, D. F. Shull, Austin 
Streyser, Willard E. Simpler, John Semple, Arthur Schwartz, 
Arthur Stengel, J. Franklin Strawinski, J. G. Spengler, Chas C. 
Schomo, R. Frank Smith, J. L. Supplee, Robert V. Smith, Carl E. 
Schlegel, Geo. Schimminger, C. M. Southall, Geo. A. Shwab, H. A. 
Spangler, Geo. M. Shamalia, Willard S. Stuck, H. W. Stuver. 

Frank C. Taylor, Henry Troemner, Frank D. Titus, M'. G. 
Tielke, G. E. Traul, J. S. Tyree, Chas. C. Trauck, Maurice W. 
Trainer, Louis Trupp, John H. Terry, C. J. Teter, Robert W. 
Tucker, Henry P. Thord, James L. Tuohy, Elliot D. Truman, Peter 
D. Tfottenstein, M. Clayton Thrush, E. S. Tyler, John K. Thum, 
C. W. Troll, Howard D. Taylor, Wilfred S. Thompson, J. Walton 
Travis. 

Walter H. Umstead, 3 Unknown Subscribers, S. E. Uhler, P. 
Henry Utech. 

J. A. Logan Vink, S. A. Visanske. 

R. W. White, Lewis E. Wilson, Willets Wilson, R. Warshawsky, 
H. E. Wilt, Harry D. Wilkinson, A. H. Wirz, Katherine P. West, 



256 Philadelphia College of Pharmacy. {^'" £^'1011''^ 

Samuel Webb, Chas. A. Weida, J. Weichselbaum, Berta Whaland, 
W. Irving Woolley, F. B. Wells, Philip S. Willingmeyer, Leo M. 
Wachtel, J. Alex. Wilhelm, Jos. L. Wade, The Walter F. Ware Co., 
Edw. S. Wright, Edw. A. Whitely, S. R. Woods, Paul D. L. Witmer, 
J. Edw. Wallis, Edyth W. Williams, Alfred C. Wood, Wm. E. 
Weiss, L. L. Walton & Co., Wm. R. Warner & Co., Fred. E. 
Winand, Thos. M. Williamson, W. B. Walter, B. C. Waterman, 
F. G. Wedemeyer, Louis Weiss, R. Willard, Walter A. Wyss, 
Paul C. H. Webb, H. Edw. Wendel, J. C. Wyatt, L Randolph 
Wehler, Alfred J. Wenner, E. Elmer Wilkins, Wm. S. Weakley, 
F. Fred. Windolph, Geo. T. Williams, Stephen D. Woolley, Harry 

E. Wertz, H. H. Whitacre, Wm. R. Warner, Jr., Claude S. Wolfe, 
Oscar C. Welsh, O. K. Whipple, J. Warren W. Worthington, H. B. 
Weiss, Chas. H. Weber, Jos. P. Williams, C. A. Weidemann, Geo. 
S. R. Wright, Allen L. Werst, John K. Wittel, Harry H. Walton, 

F. C. Weber, John C. Walton, John H. Williams, John F. Walker, 
Lewis R. Whitacre, C. E. Walmsley, Paul J. Waldner, Adam Wirth, 
Aubrey H. Weightman, William Weis, James F. White, J. Albert 
Wolfe, Harry N. Whitney, Geo. C. Webster, A. Wegener, Jos. L. 
Wiesner, A. S. Wickham, E. H. Watkins, R. C. Werner, Wm. J. 
Warner, Oliver F. Wilson, M. L Wilbert, Jos. P. Ward, Henry S. 
Wellcome. 

Benj. Franklin Young, Jos. B. Young, John K. Young, W. S. 
Young, Florence Yaple, Geo. E. Young, Benj. Lee Young, J. Frank 
Yeoly, Chas. Young, Frederick R. Yost, Nelson L. Yeakel. 

A. T. Zeller, Chas. S. Zimmerman, H. P. Ziegler. 

NAMES OF THOSE PRESENT AT THE TESTIMONIAL DINNER. 

In addition to the invitations sent to the members of the College 
and Alumni, a number of special invitations were sent to those 
prominent in educational work, and to the presidents of various 
pharmaceutical associations. While quite a number of the latter 
responded, a number, however, were unable to attend and sent 
letters containing their felicitations. These include the following: 

Mr. Benjamin T. Fairchild ; Prof. E. G. Eberle, President, The 
American Pharmaceutical Association; Mr. H. B. Guilford, Presi- 
dent, National Association of Retail Druggists ; Prof. C. Lewis Diehl ; 
Mr. F. Gutekunst ; Mr. Samuel W. Fairchild ; Governor John K. 
Tener ; Hon. Edwin S. Stuart ; Prof. J. W. Holland ; Prof. John Uri 
Lloyd ; Dr. William Muir ; Hon. J. Hampton Moore ; Hon. George 
D. McCreary; Mr. F. W. Meissner ; Prof. H. M. Whelpley; Prof. 



'^'"Mayrisn^''"'} Philadelphia College of Pharmacy. 257 

William A. Noyes; Mr. George A. Newman; Mr. Frank G. Ryan; 
Mr. H. B. Rosengarten; Prof. Edgar F. Smith, Provost, University 
of Pennsylvania ; Mr. Harry L. Stiles ; Prof. H. C. Wood ; Dr. 
Harvey W. Wiley; Dr. Robt. Ellis Thompson, President, Phila- 
delphia Central High School ; Prof. William Trelease ; Dr. William 
J. Schieffelin; Mr. Aubrey H. Weightman, Prof. John J. Abel, 
President Nicholas, Murray Butler, Dr. N. L. Britton, Samuel M. 
Clement, Jr., Prof. Charles Caspair, Jr., President A. W. Harris, 
Prof. Francis E. Lloyd, Hon. Hampton L. Carson, Dr. Samuel G. 
Dixon, Prof. W. G. Farlow, Dr. Joseph S. Neff and Hon. Wm. 
Potter. A cablegram was received from Henry S. Wellcome and 
Dr. Frederick B. Power. 

The following list gives the names of subscribers and invited 
guests that were present at the testimonial dinner at the Union 
League when the President French portrait was presented to the 
College: 

Jacob M. Baer, Edward F. Beale; W. Ward Beam, Jacob S. 
Beetem, George M. Beringer, Ralph Blum, John J. Bridgeman, 
Edwin M. Boring, H. H. Breckenridge, Miers Busch, Hon. Theodore 
Campbell, T. H. Cappeau, Edward James Cattell, William L. Cliffe, 
E. Fullerton Cook, Charles F. Dare, L. H. Davis, Hon. Murrell 
Dobbins, Thomas Donaldson, J. W. Ehman, Joseph W. England, 
George B. Evans, S. K. Felton, James A. Ferguson, Horatio N. 
Fraser, C. Dunning French, C. Stanley French, Harry B. French, 
Howard B. French, J. Hansell French, Harry Fritsch, James A. 
Garvey, George T. Gwilliam, George Haffa, A. M. Hance, John F. 
Hancock, F. H. Harmening, G. B. Heckel, Dr. Alfred Heineberg, 
Charles E. Hires, David H. Holcombe, Hibbert P. John, Hon. Isaac 
Johnson, C. Mahlon Kline, Christopher Koch, Henry Kraemer, 
Milton -i;.utz, R. H. Lackey, Chas. H. LaWall, William E. Lee, 
Charles Leedom, Joseph L. Lemberger, Robert C. Lippincott, 
Edward T. Longstreth, Clement B. Lowe, Clement W. Lowe, 
William E. Lucas, Paul L. McConomy, William Mclntyre, Rushton 
Marot, Dr. R. V. Mattison, Harry Matusow, Alfred Mellor, C. 
Carroll Meyer, Dr. Adolph W. Miller, Frank X. Moerk, Frank E. 
Morgan, H. K. Mulford, E. E. Nice, O. W. Osterlund, Dr. Ross V. 
Patterson, J. W. Rabe, J. P. Remington, Hon. John E. Reyburn, 
Howard Rohrer, Dr. George D. Rosengarten, Walter A. Rumsey, 
Saml. P. Sadtler, Dr. Nathan C. Schaeffer, Ralph C. Sharadin, 
Clayton F. Shoemaker, Richard M. Shoemaker, Walter V. Smith, 
Rev. David M. Steele, Henry C. Stewart, Dr. P. Samuel Stout, 



258 Philadelphia College of Pharmacy, {^"^■^i^y ilu"^- 

F. P. Stroup, Henry P. Thorn, Benjamin M. Thorpe, Wallace S. 
Truesdell, S. E. Uhler, Joseph L. Wade, Walter F. Ware, William 
Waterall, Dr. Charles A. Weidemann, C. T. Wetherill, W. H. 
Wetherill, Dr. William P. Wilson, Dr. Alfred C. Wood. 

COMMITTEE ON PORTRAIT. 

George M. Beringer, A.M., Ph.M., Chairman. 
Richard M. Shoemaker, Ph.G., Treasurer. 
Henry Kraemer, Ph.D., Secretary. 

Harry Vin Arny, Ph.D. R. V. Mattison, M.D. 

Jacob M. Baer, Ph.G. Caswell A. Mayo,- Ph.G. 

Wm. L. Cliffe, Ph.G. A. W. Miller, M.D. 

David Costello, Ph.G. Frank E. Morgan, Ph.G. 

Eugene G. Eberle, Ph.G. Frederick B. Power, Ph.D. 

George B. Evans, Ph.G. Wallace Procter, Ph.M. 
Benjamin T. Fairchild, Ph.G. J. B. Raser, Ph.G. 

C. Stanley French J. P. Remington, Ph.M., F.C.S. 

Harry B. Gilpin, Ph.G. Geo. D. Rosengarten, Ph.D. 

James M. Good, Ph.M. Walter A. Rumsey, Ph.G. 

L. M. Hopp, Ph.G. Frank G. Ryan, Ph.G. 

Joseph Jacobs, Ph.G. Same. P. Sadtler, Ph.D., LL.D. 

C. Mahlon Kline, Ph.B. F. L. Upjohn, M.D. 

William E. Lee, Ph.G. C. A. Weidemann, M.D. 

Jos. L. Lemberger, Ph.M. Aubrey H. Weightman 

Henry S. Wellcome, Ph.M. 

special committee on presentation. 

C. Stanley French Richard M. Shoemaker, Ph.G. 

C. Mahlon Kline, Ph.B. Walter V. Smith, Ph.G. 

Henry Kraemer, Ph.D. Otto W. Osterlund, P.D. 

Miers Busch, Ph.B., Chairman. 

In connection with this entire movement, to do honor to the 
President of the Philadelphia College of Pharmacy, many letters 
were received, which we regret we cannot take the space at this time 
to publish ; but all of these have been placed together and deposited 
with the other historical material of the College. 

The portrait has been placed in a prominent position in the 
Library of the College, and reflects credit upon the members of 
the College and Alumni who have so unselfishly and zealously 
contributed to this testimonial. Henry Kraemer, Secretary. 



Am. Jour. Pharm.l 
May, 1911. / 



Notes and News. 



259 



PHARMACEUTICAL MEETINGS. 

January meeting. — The fourth of the series of pharmaceutical 
meetings was held on Tuesday, January 18, 191 1, with Prof. C. B. 
Lowe in the chair. 

Dr. Horatio C. Wood, Jr., read a paper on " The Keeping QuaH- 
tites of Ergot and its Fluidextract," which is published in the April 
issue of this Journal (see page 172). The paper was discussed 
by Mr. W. L. CHffe, Mr. E. M. Boring, Dr. C. A. Weideman, Mr. 
John K. Thum, and Prof. Kraemer. Mr. Clifife called attention to 
the fact that the fixed oil of ergot is used to some extent in the 
preparation of certain " Hair Oils." Dr. Weideman referred to 
the value of ergot as a haemastatic in hemorrhages of the lungs. 

February meeting. — The fifth of the pharmaceutical meetings 
was held on February 15, 191 1, with Mr. Wm. M. Mclntyre in the 
chair. 

Mr. Geo. M. Beringer, Jr., presented a paper on " The Extem- 
poraneous Preparation of Medicated Gauzes," which was illustrated 
with a large number of samples, and also gave a demonstration of 
the preparation of medicated gauzes. The paper is published in 
full in the April issue of this Journal (see page 178) and ought to 
be of very great interest to Pharmacists, as well as physicians and 
shows what can be done by the retail pharmacist. These formulae 
might well be included in the National Formulary, or even be made 
official, as we find in very many of the foreign pharmacopoeias 
formulae for the preparation of medicated gauzes. The paper was 
discussed by Mr. O. W. Osterlund, Mr. E. M. Boring, and the 
chairman of the meeting. 

In the course of the discussion, one of the important points 
brought out was the superiority of the gauzes made by Mr. Beringer 
as compared with the general appearance of those found on the 
market. 



NOTES AND NEWS. 

Baseball in Colleges of Pharmacy. — When we consider the 
place that departments of physical instruction hold in our leading 
educational institutions, it is but natural to suppose that the future 
historian will consider the peculiar conditions under which this de- 
partment was introduced into colleges of pharmacy. There have been 



26o 



Notes and News. 



Am. Jour. Pharm. 
May, 1911. 



a number of brief references in this Journal to the work that the 
Philadelphia College of Pharmacy has instituted (see this Journal, 
Vol. 82, p. 545, and Vol. 83, p. 91). While all of the students of 
the College undergo a physical examination and receive instruction 
in physical culture, some of them engage in special team work. 
The baseball team of the P. C. P. played the second of what prom- 
ises to be, we hope, in the nature of an annual Harvard- Yale " 
game with the College of Pharmacy of the City of New York, at 
South Field, Columbia University, on Friday afternoon, April 14. 
We publish the following account of the game from the New York 
Sun: 

Philadelphia College of Pharmacy baseball team defeated the New York 
College of Pharmacy team yesterday afternoon for the pharmaceutical cham- 
pionship in a six-inning game, which was played on South Field, Columbia 
University, in a driving rain, the Philadelphia College of Pharmacy scoring 
7 runs, while the New York College of Pharmacy, which is an adjunct of 
Columbia, could make only 3. The druggists from the Quaker city had the 
better of it in every department of the game, and although the New Yorkers 
took the lead in the first inning, they could not hold it long, and Philadelphia 
won easily. 

The home players did their best work in the first inning, when they 
brought two runs across the plate and shut out the visitors. In the second 
session they found themselves shut out while Philadelphia made one run, 
and in the next inning another zero for New York and two tallies for 
Philadelphia gave the Quaker dispensers the lead. The game was virtually 
decided in the fourth when a batting rally, two of the hits being three- 
baggers, added three runs to the Philadelphia score. In their half of the 
inning the home players made their last run of the game, while the visitors 
made another in the fifth session. Both teams failed to score in the sixth 
and as* the players were beginning to find it almost impossible to disentangle 
their feet from the mud, the game was called. 

Hart and Gray were the stars of the game, and it was their heavy 
hitting that won the game for Philadelphia. Each made two three-base hits, 
and Hart in the fifth hit the ball hard enough for a clean home run, but 
omitted to touch third in making the circuit and was called out by the 
umpire. Hancock, who pitched for the winners, had good control of the 
ball in spite of the wet weather, and allowed only three scattered hits. New 
York used two pitchers, Steiert and Billings. All of Philadelphia's runs were 
made while Steiert was in the box. 

Yesterday's game was the second annual contest, the game last year, 
which was played in Philadelphia, also resulting in a victory for the Quakers. 

The score by innings : 

R. H. E. 

Philadelphia o i 2 3 i 0—7 7 2 

New York 2 o o i o 0—3 3 4 

Batteries— Hancock and Hart; Steiert, Bill'ngs and Neundorfer. 



THE AMEEIOAN 

JOURNAL OF PHARMACY 



JUNE, igii 



DRIED MAGNESIUM SULPHATE. 
By W. a. Puckner and L. E. Warren. 

The Committee of the American Pharmaceutical Association for 
standards of unofficial drugs and chemical products having con- 
sidered Dried magnesium sulphate " the subject was assigned 
to the senior author of this paper as referee for the preparation of 
tentative standards. Accordingly provisional academic standards 
for the substance were prepared and submitted for criticism to a 
number of manufacturers of chemicals and to several chemists 
whom it was thought would be interested. At the same time several 
brands of the product were purchased and examined. 

Dried magnesium sulphate is official in several of the foreign 
pharmacopoeias. In the Pharmacopoeia formerly official in Austria 
the method directed for the preparation of the product was to dry 
the crystallized magnesium sulphate first upon the water bath with 
stirring and then on a sand bath until a loss of 43 per cent, should be 
attained. The composition of the residual salt was supposed to 
correspond approximately to the formula MgSO^ + HoO. Such a 
salt should contain about 87.0 per cent, of anhydrous magnesium 
sulphate. In the last edition of the Austrian Pharmacopoeia it is 
directed to dry the salt on the water bath at 100° with stirring until 
36 per cent, of the original weight has been lost. The formula 
of such a salt should be approximately MgS04+2H20, corre- 
sponding to about 77.0 per cent, anhydrous magnesium, sulphate. 
The directions given by the German Pharmacopoeia (ed. 5) are to 
dry the salt in a porcelain dish on a water bath until it has lost 
from 35 to 37 per cent, of its weight. Such a salt should contain 
from 75.15 per cent, to 77.54 per cent, of anhydrous magnesium 

(261) 



262 



Dried Magnesium Sulphate. 



Am. Jour. Pbarni. 
Jnne, 1911. 



sulphate (MgSO^) yet the purity rubric demanded by this same 
authority is only 70 per cent, of anhydrous substance. The salt 
is also official in the Swiss Pharmacopoeia, the method of prepara- 
tion being similar to that prescribed in the German Pharmacopoeia 
except that the crystallized salt is allowed to effloresce in the air 
before heating. 

Dried magnesium sulphate was prepared by several methods. 
The first was by the method prescribed in the German Pharma- 
copoeia. This consists in drying the crystallized salt on the water 
bath with stirring until the substance has lost from 35 to 37 per 
cent, of the original weight. Owing to the time required it was 
found impracticable to dry the crystallized salt on the water bath 
until the specified loss had cccurred. A specimen of 50 gm. of 
the commercial salt was dried in this manner during several work- 
ing days and the loss amounted to but 33.7 per cent, instead of a 
minimum of 35.0 per cent. A duplicate lost 33.8 per cent, in 45 
hours drying. Magnesium sulphate was determined in this speci- 
men and 75.2 per cent, of the anhydrous salt found. When dried 
at 100° in the air oven for 4 hours a loss of 3.4 per cent, was 
noted in the same specimen. 

Dried magnesium sulphate was also prepared by heating 100 gm. 
of crystalHzed magnesium sulphate in an air oven, first at a tem- 
perature of 60-70° and then at a gradually rising temperature 
until the specimen practically ceased to lose weight. A loss of 
41.2 per cent, w^as noted. Several days' heating at a temperature 
of 100° with occasional maxima of 110° failed to secure a loss of 
43 per cent, as required by the former Austrian Pharmacopoeia 
(corresponding to the formula MgS04.H20). This specimen con- 
tained 84.7 per cent, anhydrous magnesium sulphate. 

The most satisfactory method of preparation was found to be to 
dry the crystallized salt at a temperature of 60-70° with stirring 
and finally at 100° until a loss of 37 to 40 per cent, had been 
obtained. A specimen so prepared which had been dried until 39.9 
per cent, of the original weight had been lost contained 81.9 per cent, 
of anhydrous magnesium sulphate. 

Three specimens of dried magnesium sulphate bearing the 
labels of as many makers were purchased on the open market and 
examined with reference to their content of anhydrous magnesium 
sulphate and to their loss when dried at 100°. Apparently as a 
protection against moisture all of the specimens purchased had 



Am, Jour. Pbarm.) 

June, 1911. i 



Dried Magiiesmm Sulphate. 



263 



been wrapped in paper before being packed in the containers. Two 
of the latter were composed of thick pasteboard and the other of 
tin with a close fitting cover. 

The magnesium, both in the laboratory specimens as prepared 
and in the specimens as purchased, was weighed as magnesium 
pyro-phosphate, the method being described in detail in another 
part of this paper. It was found that constant weight could not 
be attained when drying the commercial salt at 100° (at least dur- 
ing no reasonable length of time), the specimens continuing to lose 
weight very slowly even when dried for several days. It was 
therefore found expedient to record the results after drying for 4 
hours at 100°. 

The specimen bearing the label of the Mallinckrodt Chemical 
Works contained 67.2 per cent, anhydrous magnesium sulphate 
and lost 7.3 per cent, of water. The Powers-Weightman- 
Ro^engarten specimen contained 64.9 per cent, anhydrous magnesium 
sulphate and lost 19.4 per cent, on drying. The Merck specimen 
contained 54.3 per cent, anhydrous magnesium sulphate and lost 
26.1 per cent, on drying. While no claim for purity or strength 
is made upon the label of this specimen, the product sold by this 
firm is described in Merck's Index (1907) as containing about 2 
molecules of water, corresponding to about 77.0 per cent, of 
anhydrous magnesium sulphate. The product as actually sold, 
therefore, contains but about 70.5 per cent, of the amount of anhy- 
drous magnesium sulphate claimed for it. The results obtained 
for all of the specimens examined are tabulated below : 



Laboratory number or 
brand. 


Anhydrous magnesium sul- 
phate (MgS04) 


Water 
(Loss in 4 hours at ioo°) 


I (Ph. G. V.) 
2 


75.26 
84.68 


3-4 

Not determined 


M. C. W. 


8.2 
67.20 


Not determined 
7.29 
19.42 
26.16 


P. W. R. 

Merck 


6493 
54-27 



Tests for heavy metals and for arsenic were made upon all of 
the specimens examined by methods described in another portion of 
this paper. The result in each case was negative. 

The assertion is made in the literature that dried magnesium 



264 



Dried Magnesium Sulphate. 



Am. Jour. Pbarm. 
.hiue, 1911. 



sulphate absorbs moisture when exposed to the air and thus tends 
to revert toward the crystalHne condition. As the crystalhne salt 
is markedly efflorescent when exposed to the air (even losing as 
much as 7 to 8 per cent, of its weight) it seemed worth while to 
determine how far the dried salt would absorb moisture. Accord- 
ingly a specimen which had lost 41.2 per cent, of the original 
weight during the process of manufacture, was exposed in a hat- 
bottomed dish in a place protected from dust and a flat-bottomed 
dish containing water placed beside it. The water was replenished 
from time to time as it evaporated and the increase in weight of the 
exposed salt noted. In two months the specimen weighing 5.0027 
gm. had gained 1.8 13 gm. equivalent to 36.24 per cent, of the 
original weight. 

The examination shows that the dried magnesium sulphate on 
the American market is far from uniform in composition. This 
condition might be explained from the lack of authoritative standards 
for the product in this country. Since magnesium sulphate is 
usually administered in solution and since the dried salt contains 
only about 50 per cent, more of real magnesium sulphate (MgS04) 
than the official crystallized one it would appear that the dried 
salt is superfluous. Probably for these reasons the manufacturers 
have not considered the substance of sufficient importance to sub- 
ject its manufacture to proper laboratory control. 

Based upon the provisional academic standards as first pre- 
pared but modified as found necessary by the results of the experi- 
mental work, and by the suggestions offered by those to whom the 
provisional description was submitted for criticism,''' the following 
standards for dried magnesium sulphate are suggested : 

Dried Magnesium Sulphate — Magnesii Sulphas Exiccatus. 
Magnesium Sulphate dried at too°C. corresponding to from 77.5 
to 81.5 per cent, absolute magnesium sulphate. 

Dried magnesium sulphate may be prepared by heating (with 
stirring) 100 parts of crystallized magnesium sulphate in a tarred 
porcelain dish in a drying oven first at a temperature of 60° to 70° 
and then at a gradually rising temperature until the substance has 
lost from 37 to 40 per cent, of its weight. 

* Our thanks are due to those manufacturers and chemists who have 
made suggestions and criticisms in the preparation of the provisional 
standards for dried magnesium sulphate. 



^'"■jmie'^'iQii*™'} Permanganate Test for Cocaine. 265 

A fine white powder, without odor, and having a cooHng, saline, 
bitter taste. It is ahiiost completely soluble in water. When 
exposed to air it absorbs moisture. 

An aqueous solution of the salt (i in 40) should be neutral to 
litmus paper. 

When mixed with ammonium chloride test solution and ammonia 
water, the aqueous solution of the salt (i in 40) yields with sodium 
phosphate test solution, a white, crystalline precipitate. With 
barium chloride test solution the aqueous solution of the salt yields 
a white precipitate insoluble in hydrochloric acid. 

Ten c.c. of the aqueous solution of the salt (i in 200) should 
not respond to the time limit test for heavy metals prescribed in 
the United States Pharmacopoeia, 8th Revision. Five c.c. of the 
aqueous solution of the salt (i in 40) should not respond to the 
modified Gutzeit's test for arsenic. United States Pharmacopoeia, 
8th Revision. 

If from 0.200 gm. to 0.300 gm. of dried magnesium sulphate 
be dissolved in 50 c.c. of water, the solution filtered if necessary, 
and if 10 c.c. of ammonium chloride test solution, 10 c.c. of sodium 
phosphate test solution and sufficient ammonia water to render the 
mixture alkaline, be added in the order named, shaking after the 
addition of each reagent, the mixture allowed to stand for 12 hours, 
the precipitate collected in a tarred Gooch crucible, washed with i 
per cent, ammonia water until free from chlorides, dried, heated 
to low redness for 15 minutes, cooled and weighed, the weight of 
the resultant magnesium pyrophosphate should correspond to at 
least 77.5 per cent, of pure anhydrous magnesium sulphate 
(MgSOJ. 

From the Laboratory of the 
American Medical Association. 



THE PERMANGANATE TEST FOR COCAINE. 

By Francis J. Seiter. 

The behavior of cocaine with potassium permanganate was first 
described by F. Giesel.^ He found that the crystalline precipitate 
of cocaine permanganate is very stable compared with the corre- 



^ Giescl — Pliarm. Zeit. 1886 p. 132; also, Chcm. Ccntralbl. 1887, p. 1448. 



266 The Permanganate Test for Cocaine. {'^"j.'Ine^yii*™'' 

sponding salts of the majority of alkaloids and suggested it as a 
means of identifying cocaine. 

Allen states - that Beckurts and List, working with cold satu- 
rated aqueous solutions of the hydrochlorides of the alkaloids to 
which was added decinormal solution of permanganate, drop by 
drop, observed immediate reduction, with separation of brown 
manganese oxide, in the cases of quinine, cinchonidine, cinchonine, 
cinchonamine, brucine, veratrine, colchicine, coniine, nicotine, 
aconitine, physostigmine, codeine and thebaine. Gradual reduction 
was caused by atropine, hyoscyamine, pilocarpine, berberine, pipe- 
rine and strychnine. Morphine yielded a white precipitate of 
oxydimorphine while apomorphine immediately reduced the reagent 
with green color formation. Narceine, papaverine and narcotine 
yielded precipitates which decomposed upon addition of more 
than a few drops of permanganate. 

Recently, Saporetti found " that B-eucaine would not decolorize 
permanganate solution while the other cocaine substitutes, A-eucaine, 
nirvanine, stovaine and alipine gradually decolorized the reagent. 

In a previous paper in this Journal, it was reported that five 
drops of I per cent, potassium permanganate were immediately 
reduced by 1/2 c.c. of a 2 per cent, solution of holocaine, acoine 
and euphthalmine while gradual reduction occurred in the cases of 
stovaine, A-eucaine and B-eucaine. 

The permanganate test, as described by Giesel, was as follows : 
one centigram of the hydrochloride of cocaine was dissolved in 
one or two drops of water and i c.c. of 3 per cent, potassium 
permanganate solution was added. The precipitate of cocaine per- 
manganate formed instantly. Lyons recommended * the use of 
strong cocaine solution and decinormal permanganate. It was 
found that 2 per cent, solutions of cocaine yielded a precipitate 
after a short time, but with i per cent, solutions, the crystals only 
formed when the solution was allowed to evaporate. 

Inasmuch as the success of the test requires a considerable 
amount of cocaine, it is not surprising that Sonnie-Moret ^ found 
the reaction of no value in toxicological examinations. The test 
has, therefore, been abandoned, where small quantities of the alka- 

' Allen, Comm. Org. Anal. 2nd Ed. Vol. Ill pt. II, p. 144- 
^Saporetti. Boll. Chim. Farm., 48, 479; also Chcm. Abstr. 5, 762. 
*A. B. Lyons — Am. Jour. Pharm. 1886, 240. 

^ Sonnie-Moret, Chem. Centralbl., 1893. i P- 859. ' i 



^™ ■june'^im*'^™' } ^^'^^ Permanganate Test for Cocaine. 367 

loid are concerned, in favor of the .gold chloride and platinum 
chloride tests.*^ 

Recently, the writer has studied the action of permanganate 
solutions of various concentrations upon solutions of cocaine for 
the purpose of increasing, if possible, the delicacy of the test. 

When neutral solutions of cocaine were used, it was* found that 
the limit of precipitation was reached when the solution contained 
I per cent, of cocaine hydrochloride and this was true whether 
five drops of a i per cent, or i c.c. of saturated, permanganate 
solution was added. 

Acid solutions of cocaine hydrochloride were next treated with 
the permanganate solutions. It was found that acidity of the 
liquid favored the precipitation of cocaine permanganate. After 
several trials with various concentrations of acid and perman- 
ganate, acidity corresponding to i per cent, sulphuric acid, and a 
volume of saturated potassium permanganate equal to that of the 
cocaine solution yielded the best results. 

The test as now used in this laboratory is then as follows : 
To I c.c. cocaine solution, add one drop of 25 per cent, sulphuric 
acid and i c.c. saturated potassium permanganate solution. After 
standing some time, a drop of the liquid is removed to a slide, 
cover glass adjusted, excess of liquid removed and a drop of water 
drawn under the cover glass by means of a piece of filter paper 
placed on the opposite side. The slide is then examined under the 
microscope for the characteristic violet-red rectangular plates of 
cocaine permanganate. 

Working in the manner above described, the writer has detected 
cocaine in i c.c. of solution which contained .00033 gram cocaine 
hydrochloride, equivalent to i in 3,000. 

The other common natural alkaloids and cocaine substitutes 
above mentioned, with the exception of A- and B-eucaine, when 
treated as in the above test were instantly oxidized. The two 
eucaines reduced the permanganate very slowly. 

A-eucaine yielded very small irregular masses of violet-red 
leafy crystals in i per cent, solutions. In high dilutions (1:600) 
the crystals were better formed and resembled those of ammonium 
magnesium phosphate. The limit for the formation of the A-eucaine 
permanganate crystals is i :5ooo. 



" See Am. Jour. Phakm., Vol. 83, p. 195. 



268 



M agm a M agn esia. 



J Am. Jour. Phann. 
1 June, 1911. 



B-eucaine yielded minute violet-red globules, which did not 
crystallize on standing, in i per cent, solutions but not with lesser 
concentrations. 

The crystals were examined under a magnification of 8o 
diameters in all cases^ except the A-eucaine crystals, which required 
use of a higher power. 
Chemical Laboratory, 

Department of Health, Chicago. 



MAGMA MAGNESIA.- 
By S. L. Hilton. 

( Revj sed Form ula ) 

Magnesium Sulphate, U.S.P 350. Gni. 

Sodium Hydroxide, iig. " 

Gelatin, 150 

Distilled Water, q. s. 

1000. Cc. 

Dissolve the Magnesium Sulphate in 400 Cc. of distilled water, 
filter the solution through paper, dissolve the gelatine in 50 Cc. 
of hot water and add this solution to the Magnesium Sulphate and 
then wash the filter with several portions of distilled water using 
in all not more than 250 Cc. 

Dissolve the Sodium Hydroxide in 400 Cc. of distilled water 
and when the solution has cooled add 300 Cc. of distilled water, mix 
thoroughly and when both solutions have cooled to the room tem- 
perature, add the solution of Sodium Hydroxide to the solution 
of Magnesium Sulphate by some means that will deliver the solution 
of Sodium Hydroxide in rapid drops. Stir the Magnesium Sulphate 
solution briskly until all of the Soda solution is added, then dilute 
with distilled water to make the mixture measure 3000 Cc. 

Let stand until the precipitate has settled to the 1000 Cc. mark 
on the container, siphon of¥ the supernatant liquid and add 2500 
Cc. of water, stir well and set aside to settle again to the 1000 Cc. 



* Presented at the April, iqii meeting of the City of Washington Branch 
of the American Pharmaceutical Association. 



Am Jour Pharm.) ^ Delicatc Tcst fov AcetmiUid. 260 

June, 1911. j ' 

mark, again siphon off the supernatant liquid and add 2500 Cc. of 
distilled water, stir well and set aside to settle to the 1000 Cc. mark, 
siphon off the supernatant liquid and dilute the magma with dis- 
tilled water until it measures 4000 Co., stir well and set aside to 
settle to the 1000 Cc. mark, draw off the clear liquid, mix the magma 
well and assay by the process given, and dilute if necessary so 
that the preparation will contain 7.5 per cent. Mg (OH)o. 



ASSAY PROCESS. 

To 10 Cc. accurately measured in a cylinder and washed, with 
several portions of distilled water, into a titrating flask add two 
drops of Phenolphthalein T. S. and 30 Cc. of Normal Sulphuric 
Acid V.S. the solution is then heated to insure complete reaction, 
and titrated back with Normal Potassium Hydroxide V.S. to the 
neutral point, the amount of Normal Potassium Hydroxide V.S. 
used deducted from the amount of acid previously added gives 
the amount Normal Sulphuric Acid required to neutralize the 
Magnesium Hydroxide present, which should be at least 26. Cc. 
Normal Sulphuric Acid V.S. corresponding to 7.5322 per cent, of 
Magnesium Hydroxide held in suspension. 

With this formula and the process of assay it will be an easy 
matter to always make a product of definite strength and one that 
is always uniform. 



A DELICATE TEST FOR ACETANILID. 
By G. N. Watson, 

Assistant in Drug Laboratory, University of Kansas. 

Acetanilid when heated together with Boric Acid over naked 
flame until the Boric' Acid melts produces a yellow residue having 
a peculiar fragrant odor suggestive of Sweet Clover or Arbutus. 
The yellow color, however, is produced by either Acetanilid or 
Phenacetine. Antipyrine produces a pink color and a Naphthalene- 
like odor. Phenacetine produces an odor but characteristic of itself, 
more faint than that produced by Acetanilid or Antipyrine. With 
mixtures of the Three Antipyretics, the fragrant odor produced by 
the action of the Acetanilid is sufficient to produce the characteristic 



270 Phanuaccutical Lcs^islafioii. { ^'"■.hmrim""' 

odor, which is intensified by adchng- a few drops of water to the 
residue. 

This test suggests the use of Acetanihd as a test for Boric 
Acid, the dehcacy of which is worthy of investigation. 
March 22d, 191 1. 



PHARMACEUTICAL LEGISLATION AS APPLIED TO 
REGISTRATION AND ADULTERATION. 

By Allen C. Thomas, Esq. 

I deem it both an honor and pleasure to speak to this body of 
under-graduates. Our relationship will continue to be most pleasant 
as long as it is confined to occasions of a social, educational and 
scientific character. Far better that the pharmacist and lawyer 
meet as Knights of the Round Table than in the lists. Better to 
discuss the purposes and efi^ects of legislation in the academic forum 
than to test their authority in the legal forum. Upon the theory 
of that old pharmaceutical adage, " An ounce of prevention is worth 
a pound of cure." 

When your course shall have finished and your term of practical 
experience completed you will first apply for a certificate author- 
izing you to engage in business and thereafter your fitness will be 
determined primarily by your possession of such a certificate. The 
law requires that every proprietor, manager and qualified assistant 
having a certificate of registration shall display it in some conspicu- 
ous place in the retail drug store or pharmacy which he or she 
shall own or be employed. 

In the State of Pennsylvania the authority to grant and issue 
such certificate is vested in the State Pharmaceutical Examining 
Board. The title is somewhat suggestive of the origin and purpose 
of the Board, i.e., that of examining applicants for registration. 
To this feature of their duty I shall first direct your attention. 
Since the creation of the Board its functions have been extended 
and in addition to regulating the status of the pharmacist per- 
sonally, the regulation of his business has also been placed under 
the control of this Board and of this regulation I shall speak 
secondly, indeed the subject will naturally present itself to you in 
this order as you will first consider qualifying to hang out your 



Am. Jour. Pharm. 
June, 1911. 



PJiarmacetitical Legislation . 



271 



shingle as pharmacist and secondly, conducting and operating your 
business in accordance with the law. 

A word, therefore, concerning the Board to which you must 
shortly be introduced. It consists of five members appointed by 
the Governor from the most skilful retail apothecaries actually en- 
gaged in business in the State of Pennsylvania having at least ten 
years' experience. The Board is required to keep a book of regis- 
tration in which is reported the name and address of each and 
every person duly qualified to conduct and carry on the retail 
drug and apothecary business or to hold the position of qualified 
assistant therein. Meetings of the Board are held every three months 
at such places as they deem expedient to conduct examinations on 
the basis of which certificates are granted as the case may be, either 
to registered managers or qualified assistants : such certificate is then 
good and sufficient evidence of registration. The following require- 
ments are made of those applying for examination as qualified 
assistants, first, that they produce evidence of not less than two 
years' experience and pay the sum of $3.00 for examination and 
$5.00 for certificate and registration. For those applying for ex- 
amination of registered managers satisfactory evidence of not less 
than 4 years' practical experience and paying a fee of $3.00 for 
examination and $12.00 for registration and certificate. 

Now as to the relative effect of these two classes of certificates. 
No drug store or pharmacy can be conducted without a Registered 
Manager. The law, i.e., the Act of Assembly does not prcscril^e 
the respective rights and duties of these classes in so many words, 
but that it makes the distinction is clearly seen and therefore ])rac- 
tically leaves the determination of the matter to the constitutcl 
authority which it has empowered to enforce the Act, i.e., the State 
Pharmaceutical Examining Board. Consequently the Board has held 
that the qualified assistant is to act only in the temporary absence 
of the Registered Manager. The failure of the law to define their 
respective rights and duties as well as the difficulty of determining 
the extent of authority exercised in any particular case by the 
qualified assistant has hindered the Board in the strict enforcement 
of their views in this matter. 

The usual case of violation found is that of a Registered 
Manager who has two or more stores where he attempts to conduct 
them with only the assistance of qualified assistants, presuming that 
liis (jualification will extend authority to stores which he supervises 



272 Pharmaceutical Lccrislatioji. fAm jour Phann. 

' ( Juiu", 1911. 

but in \^ hich he is not actually engaged. Presuming this condition 
is reported to the State Board, they will at once send their Agent 
to make a purchase of some drug or to have a prescription com- 
pounded and to secure a conviction. The purchase must be made 
at a time when the Registered Manager is elsewhere. Should he 
happen to be in this store at the time or should the Agent not be 
able to prove his absence the prosecution would fail as it must be 
established beyond a reasonable doubt that there was no Registered 
Manager present at the time of such sale. 

The requirement that every drug store shall be in charge of 
a Registered Manager has been very efifectivly enforced by the 
Board throughout the State so that at present there are few instances 
of violation in the larger cities. In other parts of the State, how- 
ever, where the field is less attractive to the competent and qualified 
clerk or where detection and prosecution is difficult because of lack 
of information or inaccessibility, there are still frequently reported 
cases of attempted evasion of the law which makes necessary occa- 
sional crusades of prosecution in order to awaken the dormant con- 
science to a sense of duty and responsibility. 

Just at this point a word that may be seasonable. Many an 
appeal for a competent clerk com.es to the members of the Board 
and by reason of its familiarity with conditions generally the Board 
is in a sense an employment agency operated for the good of the 
individuals concerned and the State as well. 

Another phase in the matter which may occur to you, i.e., the 
case of a person who has no certificate or technical knowledge of the 
business owning a store. There is nothing to prevent this and 
in fact it has been decided where the question was raised in the 
case of Commonwealth vs. Zacharias reported in Volume i8i of the 
Pennsylvania State Reports, page 126, in 1897, " that the Act of 
Assembly seeks to regulate only the management of a retail drug 
store and does not prohibit a passive ownership, so in this case 
although the defendant was not a pharmacist and operated a chain 
of stores, the fact that each store was in charge of a Registered 
Manager prevented conviction and no prosecution could be sustained 
against him from the mere fact of ownership. 

The restriction of the business to such as are qualified is doubly 
effective, protecting both the public and the profession. In the latter 
case excluding those who have not earned protection through study 
and experience. The Act reads " No person shall hereafter engage as 



Am. Jour. Pharm. ) 
June, 1911. / 



Pharmaceutical Legislation. 



273 



Manager in the business of an apothecary or pharmacist or of re- 
taiUng drugs, chemicals, and poisons or to compound and dispense 
the prescriptions of physicians either directly or indirectly without 
having obtained such certificate." Just here you should note how 
complete is the language of the Act in the use of the words " com- 
pounding and dispensing." The Pennsylvania Board takes the view 
that compounding is limited to mean the assembling or mixing 
of the component ingredients, while dispensing includes all that is 
necessary to the act of filling the order and placing it in the hands 
of the purchaser. 

There are certain exceptions mentioned in this Act where drugs 
may be dispensed by others than those holding certificates. First, 
physicians so far as they supply their own patients ; second, makers 
and sellers of patent medicines, and third, storekeepers dealing in 
and selling the commonly used medicines and poisons. 

This latter exemption has been the subject of much criticism 
and it seems to me justly. The prime object of the law being to 
safeguard the community — it seems eminently proper that the sale 
of poisons at any rate should be confined tO' the competent and 
qualified pharmacist so that every sale of a poison would be subject 
to the same degree of care and regulation as that exercised by the 
pharmacist. 

The Act of 1887 after defining poison as any drug, chemical 
or preparation which, according to standard works on medicine or 
materia medica, is liable to be destructive tO' adult human life in 
quantities of 60 grains or less," required affixing to the container 
a label containing the word poison," the name of the article^ 
and the name of the seller, place of business and further that the 
seller must satisfy himself that such poison is to be used for 
legitimate purposes. In addition the pharmacist must keep a poison 
register in which is to be entered in the case of sales of poison 
known to be destructive to human life in quantities of five grains 
or less, the name of the seller, the name and residence of the 
buyer, the name of the article, quantity sold or disposed of and the 
purpose for which it is said to be intended. 

As to the first exemption in favor of physicians. I believe the 
sentiment among physicians is against dispensing their own medi- 
cines and where the allopath does supply his patients with medicine, 
it is largely because his homoeopathic brother has forced the com- 
petition, yet the physician is only paying back in kind for has not 



274 



Pharinaceutical Lcgislatio}i. 



Am. Jour. Phartu. 
June, 1911. 



the pharmacist often suggested the remedy and himself prescrihe.l 
the cure. I cannot see any particular public good to be obtained 
by the elimination of this clause. 

Respecting the other exemption in favor of preparatory remedies 
or so-called patent medicines. While no reason exists for confining 
their sale to registered pharmacists there was ample need for 
regulation of another kind and it has at last been effected through 
the regulation respecting adulteration. 

Now tO' treat of this important phase of legislation affecting the 
druggist or pharmacist, i.e., adulteration. Along this line within 
recent years there has been great development and it has followed 
generally the trend of an enactment striking at unscrupulous com- 
mercialism and constantly unmasking the wolves in sheep's clothing. 
An era of more honest dealing in drugs as well as other com- 
modities has been inaugurated and the punishment of adulteraters 
and misbranders is having a wholesome effect whereby a manu- 
facturer, seller and consumer have all been benefited. 

The first important act regulating the business of the dealer in 
drugs was that of May 24, 1887. Section 9 of this Act provided 
that No person shall knowingly, wilfully or fraudulently falsify 
or adulterate or cause to be falsified or adulterated any drug or 
medicinal substance or any preparation authorized or recognized by 
the Pharmacopoeia of the United States or used or intended to be 
used in medicinal practice nor mix or cause to be mixed with any 
such drug or medicinal substance any foreign or inert substance 
whatsoever for the purpose of destroying or weakening its medicinal 
power and effect and wilfully, knowingly or fraudulently sell or 
cause the same to he sold for medicinal purposes." And this was the 
whole law on the subject of adulteration at that date and as such 
was inadequate in view of the fact that a person so adulterating 
must be proved to have done so with a wilful and deliberate intent 
so that the enactment was intended to strike at the abuse through 
correction administered to the pharmacist for his wrongful action, 
but this was insufficient to protect the public for which reason the 
later act of May 25, 1897, passed in which the question of 
intent was eliminated and thereby the regulation made solely to 
protect the public and a fixed standard is established whereby the 
term drug is made to include any medicinal substance or prepara- 
tion authorized or known to the Pharmacopoeia of the United States, 
or the National Formulary or the American Homoeopathic Pharma- 



Am. Jour. Pharm. 1 
June, 1911. J 



Pharmac en t ical L egisla tio n . 



copoeia or the American Homoeopathic Dispensatory and the follow- 
ing five clauses enacted covering- the possible ways in which the 
adulteration might occur, i.e.: 

1. If any substance or substances have been mixed with it so 
as to depreciate and weaken its strength, purity or quality. 

2. If any quality, substance or ingredient be abstracted so as 
to deteriorate or affect injuriously the quality or potency of the 
said drug. 

3. If any inferior or cheaper substance or substances have been 
substituted in whole or part for it. 

4. If it is an imitation or is sold under the name of another 
drug. 

5. If the drug shall be so altered that the nature, quality, sub- 
stance, commercial value or medicinal value of it will not correspond 
to the recognized formulae or tests of the latest edition of the 

National Formulary," or of the " Pharmacopoeia of the United 
States," or the " American Homoeopathic Pharmacopoeia," or the 
"American Homoeopathic Dispensatory," regarding quality or purity. 

Prosecutions under this Act raised several important questions. 
In the first place you will note that the drug must correspond in 
all respects tO' the recognized formula or tests of the latest edition 
of the several authorities mentioned. Counsel seeking to make 
defense for their client charged with violation of this Act asserted 
that the Act was unconstitutional for several reasons, first, because 
it incorporated into the law a series of books hence the public were 
not informed of the text of the law except by going outside of 
the statute books whereas Article 3, Section 6 of the Constitution 
provides " No law shall be revived, amended or the provisions there- 
of extended or conferred by reference to its title only and so much 
thereof as is revived, amended, extended or conferred shall be re- 
enacted and published at length." In considering their objection 
the court held that the Act referred to certain well-known medical 
books as standards for the definition of the word drug and also 
for the definition of that which shall be deemed an adulteration of 
a drug, that this was not in any sense an attempt on the part of 
the Legislature to revive or amend a law or to extend or confer the 
provisions thereof by reference to title only. That where im- 
practicable either to publish at length the Court would not consider 
reference of this character unconstitutional. 

Again, it was argued that the act delegated the power of making 



276 



PliarinaccHtical Legislation. 



< Am. Jour. Pharm 
( .Iiiiiu, 1911. 



the law to a body other than the Legislature ; that the makers of 
the pharmacopoeia were virtually invested with leg'islative functions 
in contravention of the Constitution, Article 2, Section i, which 
provides that " the legislative power of this Commonwealth shall 
be vested in a General Assembly, etc. It is a settled axiom that 
the power conferred on the Legislature to make laws cannot be 
delegated by that department to any other body or authority." 
" Where the sovereign power of a State has located the authority 
there it must remain. The power to whose judgment, wisdom and 
patriotism this high prerogative has been entrusted cannot relieve 
itself of the responsibility by choosing other agencies upon which 
the power shall be devolved nor can it substitute the judgment, 
wisdom and patriotism of any other body for those to which alone 
the people have seen fit to confide this sovereign trust." The Court, 
however, dismissed this contention, holding that the argument was 
defective considering that the Legislature adopted a standard 
already established, that there was no delegation of authority ; that 
Act not meaning future standards, but that recognized as the stand- 
ard at the time the law was made. The latest edition, therefore, 
meant not those to be in the future, but the edition then in force 
and effect. 

This Act remained the law until the Legislature passed the Act 
of May 8, 1909 in force and effect on and after October i, of that 
year. In the meantime the National Pure Food and Drug Act of 
1906 had been passed. Much had been written and said about the 
injustice of such acts as that of 1897 where the standard was fixed 
by the several books specified in the Act from which no variation 
could or would be permitted. The objection was not made without 
reason and undoubtedly the Legislature was influenced by the 
number of important considerations to adopt what has been termed 
a variation provision so that deviation from the standard is now 
allowed provided the fact be plainly stated. It was urged that an 
iron-clad standard was un-American in that^ first, it would stifle 
research, restrict progress and destroy incentive to advancement : 
second, however far-sighted, learned and skilful were the makers of 
the standard, they had neither the whole knowledge nor the last 
word — third, that the trade would be left with valuable dead stock 
and in conclusion, that the object of the law was to give what you 
have so frequently heard called " a square deal." Hence it is that 
in the Pennsylvania Act no official drug shall be deemed to be 



^'"■j?ne''"i9n Pharmaceutical Legislation. 277 

adulterated if the standard of strength, quahty or purity be plainly 
stated upon the bottle, box or other container. Freedom of manu- 
facture and sale is thereby obtained together with the protection 
of the public by truthful statements accompanying the article. 

Certain exceptions in which there may be no variation, however, 
are specified, i.e., official preparations of opium, iodine, peppermint, 
camphor, ginger and ethol nitrite. In these instances the law is 
iron-clad and no deviation permitted. In another respect this Act 
settled a disputed point raised under the Act of 1897. Under the 
former Act certain manufacturers and dealers in this State were 
making and selling inferior preparations of standard articles but 
labelling them in a manner so different as to claim they were not 
U. S. P. For Tincture of Ginger, which is usually labelled " Essence 
of Jamaica Ginger," they made a preparation consisting principally 
of capsicum, grains of paradise or other pungent or hot drug and 
water with just sufficient alcohol to keep it from souring and a 
small quantity of ginger to impart certain of the characteristics of 
the genuine article was labelled Climax Picnic Ginger," " Gilt 
Edge Ginger," etc. So^ also an article labelled " Camphorated Oil " 
was said not to be the same as " Linimentum Camphorse," con- 
sequently the standard might be different from that required for 
the U. S. P. article, so that their article was not tO' be included in 
the class condemned, but the Court determined, as the recent Act 
has declared^ thus placing the matter beyond dispute, that an article 
shall be deemed tO' be misbranded if it be an imitation of or offered 
for sale under the name of another article. 

The important consideration under the present law is the matter 
of labelhng or branding regarding which the State Board has laid 
down certain specific requirements. The enforcement of the act is 
delegated to the State Pharmaceutical Examining Board, which, for 
this purpose, is authorized to make uniform regulations in order to 
carry out its provisions and to employ such agents, chemists, 
attorneys and assistants as may be necessary. Accordingly rules 
and regulations were at once framed, adopted and published and 
copies of the same may be secured upon application tO' any member 
of the Board. 

Hardly had the rules and regulations been promulgated when 
certain of the latter were attacked and it became a subject for 
much consideration to what extent the Board were warranted in 
going, i.e., when the article differed in strength, purity or quality 



278 



Pharinaccutical Legislation, 



Am. Jour. Pharm. 
.Tune, 1911. 



from the pharmacopoeial standard, did the language of the Act 
requiring the fact of difference to be plainly stated, justify the Board 
in requiring the use of the words " Not of official strength " and 
indeed in any instance if the vendor had printed on the label what 
was to his mind a plain statement although not in the form directed 
by the Board, might it not still be sufficient in the eyes of the law ; 
at least these are the questions very shortly to arise in prosecutions 
recently instituted by the State Board. 

At once certain manufacturers claimed that a hardship was 
imposed upon them when they were compelled to print a different 
label for every State in which their sales were made. In Penn- 
sylvania, where the regulation required the words in certain in- 
stances, Not Official Standard " necessitated the printing of a 
separate set of labels, cartons, containers, and literature, etc., for 
every sale made within the confines of the State oi Pennsylvania, 
different from that used elsewhere. To this reply was made that 
since no other State could legitimately object to this language, the 
hardship was not as great as appeared on first impression. And 
they were advised to adopt the Pennsylvania form generally. 

With changes so rapid in sO' diversified a country, with so 
many sovereign communities there is bound to be difference of 
opinion, failure to keep pace with the times ; special interests un- 
deservedly protected, all producing a lack of uniformity in legisla- 
tion and diversity in the execution of the law. Nowhere is this 
better illustrated than in the case of manufacturers who furnish 
their products to retailers in 48 different States, subject to a variety 
of legislation and still greater variety of regulation so that a general 
law enforced through uniform regulations is a consummation de- 
voutedly to be wished for, although hardly likely to be achieved 
while the States are independent sovereigns. 

Some measure of co-ordination might be accomplished by the 
general adoption by the States of the national law, then by means 
of a parliament of Pharmaceutical Boards to harmonize the various 
views and opinions represented there might be evolved a compre- 
hensive and uniform system for their enforcement throughout the 
United States. 

While this discussion in some respects wants application to 
you as individuals, yet it may offer new avenues of thought sug- 
gestions of matters concerning your brethren which the minute they 
do apply become intensely real and important. 



Am. Jour. Pharm. 
June, 1911. 



Book Reviews. 



270 



BOOK REVIEWS. 

Municipal Chemistry. A series of thirty lectures by experts 
on the appHcation of chemistry to the city, dehvered at the 
College of the City of New York. Edited by Prof. Charles Basker- 
ville, New York and London : McGraw-Hill Book Company. 1911. 

This book is the outcome of a course of lectures authorized by 
the Board of Trustees of the College of the city of New York, 
which were intended to enlighten the public as to what is being 
done for the municipality of the city of New York to safeguard 
health, facilitate traffic and add to the pleasures and comforts of 
life. While the lectures were open to the students of the college 
as well as the public, a laboratory course of instruction was provided 
for the senior student who elected the course, thus making it one 
of the most fruitful of instructive courses that have heretofore 
been attempted. At first glance the book would seem, tO' be of more 
special interest to the chemist, but it will be found of very great 
value also to pharmacists, physicians, leaders in civic movements 
and all those who desire correct information on the scientific work 
which is being done in New York City and its application in raising 
the efficiency of the people and saving the lives especially of the 
innocent. 

Allen's Commercial Organic Analysis. Vol. iv. Resins, 
india-rubber, rubber substitutes and gutta-percha, hydrocarbons of 
essential oils, ketones of essential oils, volatile or essential oils, 
special characters of essential oils and tables of essential oils. 
Fourth edition, entirely rewritten. Edited by W. A. Davis and 
Samuel S. Sadtler. Philadelphia: P. Blakiston's Son & Co. 191 1. 

This is another of the volumes of Allen's Commercial Organic 
Analysis that will be welcomed by pharmacists who desire to be 
kept informed on the newer analytical methods which may be 
employed in the testing of the products which they handle. The 
monograph on the Resins." is the work of Dr. M. Bennett Black- 
ler and in it will be found very many useful hints regarding the 
examination of such commercial products as asafetida, turpentine, 
colophony, mastic, etc. The chapter on " India-rubber, Rubber- 
substitutes and gutta-percha " has been written by E. W. Lewis 
and of course will be especially valuable to the analyst who engages 
in the somewhat difficult work of examining rubber compounds. 



28o 



Book Revieivs. 



f Am. Jour. Phaini. 
\ Juue, 1911. 



Dr. T. Martin Lowry is the author of the chapters deahng with the 
hydrocarbons and ketones of essential oils " ; Mr. Ernest C. Parry 
has prepared the general monograph on volatile or essential oils 
while the special characters of the individual essential oils " has 
been left in the hands of Dr. Henry Leffmann and Prof. Charles 
H. La Wall. While probably nothing, that has been done in the 
study of essential oils, can compare with the publications of 
Schunniel & Co., yet the subject is one of such great imix)rtance 
that analysts welcome the contributions from all practical writers, 
particularly when methods and results are presented in a readily 
available form as we find them in this volume. 

A Research on the Pines of Australia. By Richard T. 
Baker, F.L.S., and Henry G. Smith, F.C.S. Published by author- 
ity of " The Government of the State of New South Wales." Sid- 
ney : William Applegate Gullick, Government Printer. 1910. 

This is another one of those comprehensive and illuminating 
publications that has emanated from the Technological Museum, 
New South Wales. Here are two earnest workers, who are dis- 
tinguished by reason of their earlier work on the Eucalypts and 
their essential oils " (see this Journal^ Vol. 76) and who have now 
completed a self-imposed and arduous task " which was made pos- 
sible by the help and assistance of the higher officers of the Depart- 
ment of Public Instruction. This recent work of Baker and Smith, 
like their previous monograph on the Eucalypts will endure and 
is an example to individuals and governments if they would do 
something that is worth while. As Linnaeus well said in one of 
his addresses while professor in the University of Upsala, to 
do great things one must leave little things alone." 

The authors state that of the 32 genera described in Bentham 
and Hooker's Genera Plantarum/' 1 1 are found in Australia and 
Tasmania. As a result of their studies these genera are presented 
in the following sequence: Callitris with 18 species; Actinostrobus 
Vvath 2 species; Disclma ( Fitzroya) and Microcachrys, each with 
one species; Athrotaxis with 3 species; Araitcaria and Agathis 
with 2 species each; (Dacrydium) with i species; Pherosphcera 
with 2 species ; Phyllocladus with i species, and Podocarpus with 
5 species. 

It is of interest to note that while the work is entitled " A 
Research on the Pines of Australia," not a single representative of 



Am. Joui'. Pharm. 
June, 1911. 



Book Revieivs. 



the Ahieteae, which includes tlie genus Pinus with its 70 or 80 
species and having the greatest geographical range of the whole 
order," is found in the territory covered by the authors. 

The order of investigation has been as follows: i. Historical 
botany of the species. 2. Systematic descriptions. 3. Leaves and 
fruits : a, economics ; b, anatomy ; c, chemistry of the oils. 4. 
Timber : a, economics ; b, anatomy ; c, chemistry of its products ; d, 
forestry. 5. Bark : economies ; b, anatomy ; c, chemistry of its 
products. 6. Illustrations, to aid in the study of the letterpress. 

In summarizing their results the authors state that " botanically 
the results of the research were generically greater than those 
specifically, for the peculiarities of structure were found to be 
quite characteristic of, and differing from, those of cognate genera. 
Chemically and economically they promise to be of great importance 
and to open up new fields of commercial enterprise." 

They reiterate their belief in taxonomic work which considers 
the chemical properties and physical characters of the plant con- 
stituents along with botanical characters, and state species so 
founded give practically constant results, and preserve specific 
characters throughout their geographical distribution." On this 
basis they divide the species of the large genera Callitris into three 
groups and give a table showing the probable evolution of the 
species. 

Several new compounds are reported as present in the Australian 
Coniferales, but perhaps the most interesting discovery is that 
of a manganese compound in practically all of these trees, and 
which the authors believe is an essential constituent of them. 
This compound gives to the wood a darker color and corresponds 
to what has been regarded as resin " by previous workers. 

The illustrations are very numerous and very excellent, being 
half-tone reproductions of the living plants, photo-micrographs 
and color plates of microscopic sections. 



282 



Progress in Phanuacy. 



J Am. Jour. Pharm 
1 .laii«, 1911. 



PROGRESS IN PHARMACY 

a quarterly review of some of the more interesting liter- 
ature relating to pharmacy and materia medica. 

By M. L Wilbert. 

The first anniversary of the United States Pharmacopoeial 
Convention appears to have been the occasion for an unusual 
number of interesting happenings bearing- on the Pharmacopoeia 
of the United States, its scope, uses, standing in law and the 
progress of the present revision of the book. 

Not the least important of these several items is the renewed 
interest that is being manifested in the scope of the Pharmacopoeia 
and the possible uses of the book as a basis for rational instruction 
in materia medica. 

Dr. Arthur Dean Bevan, in his address as Chairman of the 
Council on Medical Education of the American Medical Association, 
in referring to this need says : 

" A limited list of drug preparations containing' only those 
which are most useful and important, is of particular value to 
medical education at the present time. With the overcrowded 
condition of the medical curriculum, it is highly important that 
the small amount of time which the student has to devote to the 
study of drug preparations should be largely spent in obtaining 
a thorough knowledge of the more important drugs rather than 
in the obtaining of a superficial knowledge of all drugs, the ma- 
jority of which are of little or no value." 

The members of the Association of American Medical Colleges, 
present at the annual meeting held in Chicago in Eebruary, 1911, 
also discussed the various phases of the same question and unani- 
mously adopted a resolution asserting that the use of a small but 
representative group of medicaments in teaching pharmacology and 
materia medica is conducive to scientific progress in therapeutics. 

U.S. P. Scope. — An editorial (/. Am. M. Ass., 1911? v. ^6, p. 
1269) discussing the scope of the next Pharmacopoeia, asserts that 
although the Committee of Revision of the United States Pharma- 
copoeia was appointed nearly a year ago, it has issued no report 
to show what progress has been made, and points out that the 
Committee should realize that the medical profession is interested 
as never before as to what should be added to, or deleted from. 



^™jmir'im*™' } Progress in Pharmacy. 283 

the next edition of the Pharmacopoeia. Physicians frequently accept 
at their face value claims made by interested persons regarding the 
therapeutic action of certain drugs, and there is a tendency on the 
part of certain doctors to prescribe such drugs, even after they 
have been admitted to the official standard and consequently in- 
cluded in text-books. 

Another editorial (/. Am. M. Ass., 191 1, v. 56, pp. 1198-1199) 
in discussing the standardization of digitalis, asserts that one of 
the greatest handicaps to exact drug therapeutics is the fact that 
impressions " either of the physician or of the patient play such 
an important part. Many other branches of medicine have been 
put on a truly scientific basis as a result of careful quantitative 
work, in either the laboratory or the clinic, or in both, but in drug 
therapeutics, such expressions as " the drug seemed to do good," 
are constantly used without the slightest attempt to measure any 
tangible effect, or tO' compare the case under treatment with one 
running a natural course. 

A suggestion of the widespread confidence in so-called clinical " 
observations is embodied in the remarks of a reviewer in the 
British Medical Journal, who, in dealing with the fifth edition of 
Professor Cushny's book, says: 

We cannot close the book without feeling how great would 
be the advantage to medicine if such an authority as Professor 
Cushny could be provided with access to the wards of a hospital, 
so that his profound pharmacological knowledge should receive 
more of the clinical ' salt,' which could not fail to render it the 
more serviceable." — Chem. and Drug., 191 1, v. 78, March 18, p. 50. 

Scope of the German Pharmacopceia. — Ernst Gilg, in com- 
menting on the drugs in the Ph. Germ. V, asserts that the one 
exception that he has to make is that the revisers of the Pharma- 
copoeia, in selecting articles to be included in the book, have shown 
a woeful lack of system. He expresses the belief that it is about 
time that books of the importance of pharmacopoeias be divorced 
from personal likes and dislikes, and that the scope at least be 
based on broad general principles that should be followed through- 
out. — Ber. d. pharm. Gesellsch., Berk, 191 1, v. 21, p. 11. 

Importance of the Pharmacopceia. — Oscar Oldberg, in an 
address on the importance of the pharmacist to mankind, makes 
a number of reasonable and sane statements regarding the scope 
of the Pharmacopoeia. He points out that the very life of pharmacy 



284 



Progress in Pharmacy. 



Am. Jour, Phann. 
.lime, 1911. 



depends upon the Pharmacopoeias, and asserts that the pharmacists 
of America have contributed much to make the Pharmacopoeia of 
the United States respected. Upon examination it is found that the 
National Pharmacopoeias, whatever else they may contain, include 
the longest knov^n and most thoroughly tested drugs and medi- 
cines which, having won and retained the approval of the medical 
profession, may be said to represent the " survival of the fittest." 
In that respect the Pharmacopoeias are admirable. Nearly all of 
the twenty national Pharmacopoeias, however, have published and 
do publish recipes for quack nostrums which men ought to know 
are used only by the very ignorant. Some of the nostrums put 
in the Pharmacopoeias a century ago when actually employed by 
those who then practised the art of healing are still retained in 
these books in this age of highly developed medical knowledge 
when physicians treat them with the contempt such rubbish merits. 
— Bulletin of Pharmacy, May, 191 1, pp. 202-203. 

U.S. P. AS A Legal Standard. — As a part of their defense in 
a suit under the provisions of the Food and Drugs Act, Lehn & 
Fink enter a demurrer in which the constitutionality of the Food 
and Drugs Law is attacked on three separate and distinct grounds, 
which, briefly, are as follows: (i) Because it delegates legislative 
power, which under the Constitution of the United States belongs 
exclusively to Congress, to changing, private bodies, not created 
by, or subject to, the control of Congress. (2) Because it is an 
ex post facto law in that it specifies that the Pharmacopoeia used 
must be one "official at the time of investigation," and (3) because 
the act seeks to deprive a citizen of his property and liberty without 
due process of law. — Oil, Paint and Drug Reporter, March 6, 

In overruling the demurrer of the defendant. Judge Hough 
points out that the food and drugs act merely decrees that medi- 
cines must conform to the implied standards under which they were 
sold; that if they were sold under the titles of the Pharmacopoeia 
and the National Formulary they must conform to the standards 
embodied therein and that this does not constitute a delegation on 
the part of Congress of its legislative functions to an irresponsible 
body. In overruling the second contention Judge Hough hek„ 
that the phrase " official at the time of investigation " must be 
held to mean official " at the time the goods are shipped," re- 



^"'j^Srim*'^'"'} Progress in Pharmacy. 285 

gardless of when the actual analyses or examination might be 
made. — Ihid., March 27, 191 1, p. 9. 

Digest of Comments. — The volume of Digest of Comments 
on the Pharmacopoeia of the United States of America (Eighth 
decennial revision) and the National Formulary (Third edition) 
for the calendar year ending December 31, 1908, has just appeared 
as Hygienic Laboratory Bulletin No. 75. The book comprises a 
total of 564 pages and, in addition to references to criticisms on 
the pharmacopoeia, also includes practically all the available refer- 
ences on the origin, composition and uses of official articles. As 
a reference book for the active worker in branches related to phar- 
macy this volume should prove to be of value, while for those directly 
interested in the Pharmacopoeia and the National Formulary, the 
book should be an inexhaustible mine of suggestions for practical 
work and original investigations. 

Prof. Oldberg. — The remarks by Prof. Oldberg referred to 
above were made in connection with the celebration of the twenty- 
fifth anniversary of the School of Pharmacy of the Northwestern 
University, at which time Prof. Oldberg celebrated the twenty- 
fifth anniversary of his connection with the school, and retired 
from the deanship because of his continued ill health. To' American 
pharmacists who have had the pleasure of meeting Prof. Oldberg, 
his enforced retirem'ent from active work at this time will appeal 
as a great loss to American Pharmacy. Prof. Oldberg occupies 
a peculiar and altogether unique place in American Pharmacy and 
his ideals will no doubt serve as an inspiration tO' future generations. 
To those who' have had the pleasure of meeting Prof. Oldberg, his 
quiet and dignified strength, his clear foresight and his positive 
ways will long appeal. His many friends who were unable to 
take part in the well-merited tribute recently paid him in Chicago 
will join in wishing him many years of continued activity for the 
uplift of American Pharmacy. 

New School of Pharmacy. — A news item in a recent number 
of the Druggists Circular (May, 191 1, p. 269) contains the an- 
nouncement of a proposed department of pharmacy in connection 
with the Fordham University School of Medicine. The course 
as outlined will lead to two degrees, that of bachelor of pharmacy 
ind that of doctor o'f pharmacy. The bachelor's degree will 
leq-iire attendance during three full terms aggregating 1,475 hours 
of instruction, and the subjects taught will include : general, 



286 



Progress in Pharmacy. 



(Am. Jour. I'harm 
\ June, 1911. 



analytical, organic, and pharmaceutical chemistry, physics, botany, 
zoology, materia medica, pharmacy, bacteriology, experimental 
pharmacology, food and drug examination and clinical pathology. 
The subjects of instruction for the doctor's degree will include 
all of the above together with physiology, physiological chemistry 
and hygiene ; attendance at anatomy lectures, demonstrations and 
recitations will also be required. 

While, theoretically, this proposed course in pharmacy would 
be a decided and timely forward step in pharmaceutical education, 
there can be no question as to the impracticability of attempting 
to develop a really high-class course in pharmacy unless the uni- 
versity itself is in position to adequately endow the school so as 
to make it entirely independent of the fees to be secured. 

Medical Education. — An editorial commenting on an article 
in the Wiener Klinische Wochenschrift, on American Medical 
schools points out that the diploma mill and the commercial medical 
school are unknown in Europe. The ignorant but mercenary 
physician is justly regarded there as a grave social danger. In 
these directions we have much to learn from Germany. Only by 
the establishment and maintenance of high standards of medical 
education can we hope to retain the respect of other nations and 
to effect those speedy and radical reforms " which conditions 
demand. — /. Am. M. Ass., 1911, v. 56, p. 1043. 

Present Day Conditions of Pharmacy. — In an address de- 
livered at the joint meeting of the Wayne County Medical Society 
and the Detroit Retail Druggists Association, Henry P. Hynson 
of Baltimore, asserts that the hindering practices that retard the 
accomplishment of idealistic conditions, in the practice of pharmacy 
are largely due to incompetency on the part of pharmacists, and the 
inability on the part of some of the physicians to appreciate credit- 
able pharmaceutical attainments or to dififerentiate between the true 
and false in pharmacy. 

In commenting on the political drawbacks to progressiveness in 
Pharmacy, he asserts that the American Pharmaceutical Associa- 
tion has not had the support and interest of pharmacists it deserves. 
It needs stirring up ; its enemies, if it has any, are not sufficiently 
active to give it healthy exercise. It is cursed with politics, con- 
servative, self-preserving, holding back politics, not that " go ahead," 
do something " kind, which has made so much out of the American 
Medical Association and done so much with it. That kind of 



Am. Jour. Pharm. 

June, 1911. 



Progress in Pharmacy. 



287 



politics, if it is politics, would do the American Pharmaceutical 
Association good, a good deal of good. — A^. A. R. D. Notes, May 11, 
P- 335- 

Los Angeles Meeting of the American Medical Associa- 
tion. — The issue of the Journal of the American Medical Asso- 
ciation for May 20, 191 1, appears as the Los Angeles number, and 
in addition to a number of illustrations and a description of the 
City of Los Angeles, also contains the preliminary programme for 
the section meetings. From the number of papers to be presented 
it would appear that the Los Angeles meeting of the American 
Medical Association will be not only an unusually interesting one, 
but also well attended, and if the preliminary programme is an 
indication of the possibilities of the meeting itself the latter should 
be epoch-making. 

Reformed Almanac as a Health Evangelist. — An editorial 
(/. Am. M. Ass., 191 1, V. 56, p. 11 15) calls attention to the January- 
February number of the Virginia Health Bulletin which is issued 
in the form of an almanac and quotes a number of advisory 
aphorisms such as " A dirty well is more dangerous than a dirty 
kitchen," Good water is one of the best insurance policies a family 
can carry," " Wire screens in the window keep crape from the 
door," " A light overcoat is better than a heavy cold," " It is better 
to sleep in the fresh air than the fresh grave," and concludes that 
the Virginia Department of Health deserves hearty congratulations 
for its success in reforming one of our oldest family institutions and 
converting it into an evangel of health. 

The " World " Sensation. — The sensational charges of in- 
competency and criminal carelessness of retail druggists brought by 
the New York World have been liberally discussed in drug journals, 
both in this country and abroad. 

Xrayser H, in commenting on the so-called " expose " believes 
that rubidium iodide is just about " the limit " as a test for the 
accuracy of dispensing. He thinks such a test prescription could 
not have been better chosen if the New York World had intended to 
defeat the very object which it had in view, and in one sense this 
is satisfactory, for the campaign to prove that druggists as a class 
are inaccurate or careless dispensers or willfully fraudulent was 
unworthy to start with. — Clicni. and Drug., 191 1, v. 78, April 29, 
p. 115. 



288 



Progress in Pharmacy. 



Am. Jour. Pharni. 
Jime, 1911. 



Patent Medicines and Price Protection. — An unusual 
amount of publicity has been given to- the Supremie Court decision 
in connection with the direct contract price ])rotcction plan of the 
Dr. Miles Medicine Company. 

The publicity that has been given to the decision in the lay 
journals cannot be said to be creditable to or of advantage to the 
best interests of the drug trade generally. The Druggists Circular 
(May, 191 1, p. 238), in commenting on the evident tendency of 
the proprietary medicine branch of the retail drug business says : 

" The retail drug trade has many heavy loads to carry at best ; 
it should not unnecessarily handicap itself by appearing as a sup- 
porter and defender of the makers of nostrums whose sale is re- 
garded as ' contrary to public policy.' 

Proprietary Medicines in the United States. — W. A. Puck- 
ner, in an article published in ''Progress/' (London, England, April, 
191 1 ), discusses the proprietary medicine situation in the United 
States, and points out that in many respects we in this country 
are far ahead of England and some of the continental countries in 
combating the proprietary medicine evil. This is particularly true 
of proprietary medicines supplied through physicians. Even the 
leading medical journals in Great Britain and on the continent of 
Europe generally, accept advertisements of the patent medicine type 
of proprietaries, while in the United States many if not all of the 
medical journals have eliminated from their advertising pages at 
least the worst of this type of preparations. 

Coca Cola Case. — An unusual amount of space has been de- 
voted in American drug journals to the discussion of the now 
famous coca cola case. The Druggists Circular (May, 191 1, v. 55, 
p. 274) reports that Judge Sanborn, who was conducting the trial, 
decided that the Government had failed to establish an actual 
violation of the letter of the food and drugs act by the coca cola 
manufacturers, and dismissed the case. One of the most interesting 
features of the trial was the large array of expert witnesses on 
each side. The case fell through, seemingly, because of a confusion 
in the minds of some of the prosecuting witnesses between what 
the law actually prohibited and what they thought it ought to 
prohibit. 

N.N.R. — To insure a more wide-spread distribution of N.N.R. 
the American Medical Association has included a reprint of this 
publication as a supplement to the Journal of the American Medical 



Progress in Pharmacy. 289 

Association for April 15, 191 1. The supplement includes all of the 
material published in N.N.R. and a complete index which makes 
the pamphlet available for reference. 

An editorial (/. Am. M. Ass., 191 1, v. 56, p. 11 12) commenting 
on the publication, reviews the history of the Council on Pharmacy 
and Chemistry, and recommends that the supplement be critically 
examined and especially is it urged that physicians read the rules 
which are printed in the front of the book, bearing in mind that 
these rules represent the principles on which a preparation is 
accepted or rejected. 

Ph. Germ. V. — The new German Pharmacopoeia has been per- 
haps more actively discussed in European drug and pharmaceutical 
journals than any Pharmacopoeia published up to the present time. 
Much of this discussion has been of a critical nature and some of 
it caustic, but all of it nO' doubt will prove beneficial either directly 
or indirectly and should go far toward making the next edition of 
the German Pharmacopoeia even more representative of the best in 
the practice of medicine and pharmacy. 

A recent article in the Chemist and Druggist (1911, v. 78, 
April 29, pp. 139-142) discusses the new galenical preparations that 
have been included in the Ph. Germi. V, and points out that only a 
limited number, soriie 20 in all new galenical preparations are 
represented in this Pharmacopoeia. 

Canadian Formulary. — An editorial review of the third edition 
of the Canadian Formulary of Unofficial Preparations, published 
by the Authority of the Ontario College of Pharmacy, in the 
Chemist and Druggist (1911, v. 78, April 29, pp. 146-147) calls 
attention to some of the many changes and reprints a number of 
new recipes and alterations. 

Metric Prescriptions.— The conclusions of the Council of the 
British Medical Association on the adoption of the metric system 
of weights and measures by medical practitioners in i)rescribing and 
dispensing, are reprinted {Pharm. J., Lond., May 6, 191 1, p. 585) 
as follows : 

" The Council recognizes that the full and complete adoption 
of the metric system in practice depends upon its being made the 
system according to which students are trained, and therefore 
recommends that the teaching, both theoretical and practical, in 
pharmacology and materia medica, should henceforth be according 
to the metric system." The Council also outlines a transitional 



Am. Jour. Pharm. 
.June, 1911. 



290 



Pro ogress in PJiarmacy. 



Aiu. Jour. Pharin. 
June, 1911. 



procedure suggested for adoption by medical practitioners and 
presents the following recommendations : 

1. That the teaching both theoretical and practical in pharma- 
cology and materia medica should henceforth be according to the 
metric system. 

2. That medical practitioners should now write their prescrip- 
tions in metric form, and that, tO' facilitate this, mixtures should be 
ordered in sixteen-dose bulk, and pills or powders should be ordered 
in tens. 

3. That dispensers should be instructed that every prescription 
written without symbols is to be dispensed in metric measures. 

4. That the divisions should take the matter into consideration, 
and, if they think desirable, confer with the pharmacists in their 
area. 

Pharmaceutical Preparations. — The chemical laboratory of 
the American Medical Association {/. Am. M. Ass., 1911, v. 56, 
p. 1344) presents an additional contribution on commercial tablets 
of bismuth, opium, and phenol, and graphically illustrates the com- 
position of these tablets as claimed by various manufacturers and 
the composition actually found in the laboratory. 

An editorial in the same Journal (pp. 1 334-1 335) points out 
that for some years past pharmaceutical houses have put out in 
tablet form an enormous number of combinations of drugs of real 
or fancied value. In many instances the combinations are not 
suited to the tablet form and it is not surprising that many of 
these tablets do not conform to the composition that is claimed for 
them. It is not to be inferred that the manufacturers willfully 
put up products that are false to label, but rather that many of 
the combinations are pharmaceutical impossibilities. That is to say, 
it is pharmaceutically impossible — or at least commercially imprac- 
ticable — to manufacture, in tablet form some of the combinations 
that are listed in the manufacturers' catalogues. 

Doses. — An editorial (/. Am. M. Ass., 1911, v. 56, p. 11 14) 
discusses the determination of the proper dose of medicine and 
quotes from Manquat's " Principles of Therapeutics " his opinion re- 
garding the fallacy of undue dependence on medication. The edi- 
torial concludes that the principles as stated are correct. The drug 
is to be regarded only as a staff to assist lightly over the difficult 
places, and not as a strong crutch to bear' the whole burden. First, 
throw away the pack and the other impediments ; give entire 



Am. Jour. Pharm. 
June, 1911. 



Progress in Pharmacy. 



291 



freedom of action to all natural forces ; assist by the staff only as 
actually needed and the steep will be surmounted. 

Adrenalin. — A news note {Oil, Paint and Drug Reporter, 
May 8, 191 1, p. 28H), points out that in the final hearing on the 
alleged infringement of the Takamine patents on glandular ex- 
tractive products, Justice Hand of the United States Circuit Court 
found for the complainant on nine of the sixteen claims in the 
patent specifications in question, in one cause of action, and on 
four of the eight claims in the other cause. The news item also 
points out that not all of the claims of either patient were at issue, 
and that Justice Hand held that the case had to do only with the 
patent on the product and not that on the process. 

Epinephrine. — An editorial in discussing the need for a generic 
name for the blood-pressure-raising substance of the suprarenal 
gland, points out that there are thirty or more different brands of 
solution of this substance on the market, five being in this country 
alone. The products are identical so far as their chief constituent 
is concerned ; they differ, however, as to the solvent and preserva- 
tive used. The processes of manufacture of some of them are 
patented ; all of them are sold under trade names. The editorial 
concludes that it cannot be too strongly emphasized that " Epine- 
phrine " is a true scientific name for the active principle of the 
suprarenal gland, and that it should be used on all occasions when 
the active principle and not some particular firm's make is referred 
to. — J. Am. M. Ass., 191 1, v. 56, p. 901. 

Aspirin, — ^The Bayer Co., Ltd., in discussing trade-mark rights, 
points out that as a rule an important trade-mark is the property 
of a wealthy firm, but none the less it is something that has to be 
worked for ; behind it there is brain and there is energy, and it has 
had to be paid for. The law supports its rights, and anyone infringing 
them does so at his peril. — Pharm. I., Lond., 191 1, v. 86, March 11, 

p- 358. 

M. Meldrum, in a communication in which he discusses the 
abuses that have grown out of trade-mark rights in England, 
asserts that honesty, commercial honesty at least, has become more 
or less relative. He contends that the royalty or profit of trade- 
marked articles is out of all proportion to the price paid and the 
modicum of brain and energy supplied by the holder of the trade- 
mark, and thinks it high time to consider the possibility of placing 
some check on the present methods of granting trade-marks or 



292 



Progress in Pharmacy. 



/ Am. Jour, Pharm. 

I June, , 1911. 



trade-names in so far as the practice of pharmacy is afifected there- 
by. — Ibid., March 25, p. 424. 

Benetol. — An unsigned article in the " Propaganda for Re- 
form " discusses the claims that are being made for benetol, and 
concludes that the claim made in the advertising matter that benetol 
is a newly discovered compound is absurd. It is not a chemical 
compound but a simple solution of the well-known substance 
alphanaphthol in the still better-known substances, glycerin, soap 
and water. — /. Am. M. Ass., 191 1, v. 56, pp. 1128-1129. 

Caffeine. — The article on Therapeutics in the Journal of the 
American Medical Association for May 6, 191 1 (v. 56, pp. 1328- 
1331) is devoted to a discussion of the therapeutics of cafTeine. 
The history of this chemical is reviewed and the pharmacology 
and therapeutics discussed at some length. Caffeine-containing 
drugs such as guarana and kola are also discussed. 

Cargentos. — Cargentos is claimed to be a preparation of col- 
loidal silver containing 50 per cent, of metallic silver in the form 
of oxide, together with a sufffcient amount of modified casein to 
maintain the silver oxide in colloidal form when in solution. 

Cargentos is prepared by precipitating an alkaline solution of 
silver caseinate and silver oxide by an acid, dissolving the precipi- 
tate in an alkali, dialyzing the resulting solution against running 
v^^ater and evaporating the remaining colloidal solution to dryness in 
vacuo. — /. Am. M. Ass., 191 1, v. 56, p. 1460. 

Colchicine. — Hermann Fiihner {Archiv filr Experimentelle 
Path. u. Pharm.) considers it necessary to apply biological as well 
as chemical tests for toxicological determinations of colchicine, since 
colchicine resists the putrefactive processes of the dead body for 
several months and certain animal decomposition products give 
color reactions similar to those of the alkaloid. 

Cycloform. — Cycloform is the isobutyl ester of p-amidobenzoic 
acid, which forms a white crystalline powder, slightly soluble in 
water, easily soluble in alcohol, ether and benzene. It is a powerful 
local anaesthetic, and has but little toxic action. It is recommended 
in the form of a 5-per-cent. ointment or dressing, and is useful 
in certain skin diseases. — Chem. and Drug., 191 1, v. 78, April 29, 
p. 151. 

Digitalis. — An editorial (/. Am. M. Ass., 191 1, v. 56, pp. 
1198-1199) in discussing the standardization of digitalis, calls atten- 
tion to Hyg. Lab. Bull. No. 74, in which Hale points out that the 



Am. Jour. Pharm. 
June, 1911. 



Progress in Pharmacy. 



293 



view adopted by most pharmacopoeias and by the Brussels Con- 
ference that leaves of the second years' growth are more potent than 
those of the first year appears to be founded on tradition only. The 
view, or rather impression, that the leaves of wild growing plants 
are more potent than those of the cultivated plants also does not 
rest on a scientific basis. The editorial concludes that a perusal 
of this Bulletin will place the practitioner in a much better position 
to form a judgment of the character of the digitaHs preparation he 
uses and that the work which it embodies should be of value in 
improving the pharmacopoeial requirements of this important drug. 

DiGLYCODiSALiCYLic AciD. — ^It is claimed that diglycodisalicylic 
acid 0(CH2.COOC6H9.COOH)2, possesses the full physiological 
activity of salicylic acid, and has certain advantages over acetyl- 
salicylic acid for therapeutic use. It forms shining, odorless leaflets, 
with a faint acid taste; it melts at 168-170° C. — Pharm. J,, Lond., 
191 1, V. 86, April 15, p. 498. 

OvoGAL. — Ofvogal is a combination of bile acids with egg 
albumen. It is a greenish yellow powder, insoluble in water, dilute 
acids, ether, benzol, fats, etc. Alcohol and acetone do not dissolve 
it, but after long action remove from it small amounts of the bile 
acids. Alkalies dissolve ovogal, splitting it into albumen and bile 
acids (Glycocholic acid and taurocholic acid). — /. Am. M. Ass., 
191 1, V. 56, p. 1460. 

Oxygen. — A report of the Council on Pharmacy and Chemistry 
outlines a description with tests for compressed oxygen (/. Am. M. 
Ass., 191 1, V. 56, p. 813). An editorial (ibid., p. 820) points out 
that this report describes an article which so far is one of the few 
things that have not been appropriated by the proprietary medicine 
houses. Oxygen is often depended upon to save life that is at its 
lowest ebb, and the purity of the substance is a most important 
matter, more important than the purity of many official drugs. 

Peristaltin. — ^Peristaltin is a glucoside of the formula 
Cj^H^gOg, extracted from cascara sagrada. It is a yellow powder, 
soluble in water and in dilute alcohol. It is said to have a marked 
purgative action. — Chem. and Drug., 191 1, v. 78, April 29, p. 151. 

Phenol. — An interesting controversy has grown out of the 
Ph. Germi. V requirement that phenol should react neutral with 
litmus paper. Ernst Schmidt {Arch. d. Pharm., 1911, v. 249, pp. 
236-240) discusses some of the attacks that have been made on 
the pharmacopoeial statement, and points out that while ordinary 



294 



Progress in PJianuacy. 



jAiu. Jour. Pharm, 
I June, 1911. 



crystalline carbolic does react distinctly acid with litmus paper, it 
is readily shown that this reaction is not due to phenol but to a 
contaminating acid, and that ordinary phenol when neutralized with 
a few drops of alkali, and absolutely pure phenol will comply fully 
with the Ph. Germ. V requirements. 

Pantopon. — A report of the Council on Pharmacy and Chem- 
istry (/. A}ii. M. Ass., 191 1, V. 56, pp. 1278-1279) discusses 
pantopon, and points out that this is a preparation of opium, 
containing a mixture of hydrochlorides of the various opium alka- 
loids, as extracted directly from the drug with more or less purifica- 
tion. The Council holds that the name does not effectively suggest 
that the preparation is a ntixture of opium alkaloids and that it 
does not protect the public against habit-forming and other dangers 
inherent in such mixtures. 

Papine, a more or less similar preparation, is also commented 
upon, and an editorial (p. 1268) concludes that pantopon and papine 
are a menace to the public, and that in spite of the testimonials 
for both these products it would not be amiss if physicians would 
continue to use the drugs, morphine and opium, whose value — 
and dangers — they know. 

Phosphorus. — An editorial discussing the possible elimination 
of white phosphorus in the production of matches, points out that 
there are about 3,500 employees in 15 of the 17 match factories in 
the United States. Of 3,383 whose occupation was specified 65 
per cent, are exposed to phosphorus fumes ; 95 per cent, of the 
1,395 women are so exposed. An intensive study of 3 factories 
was made, and eighty-two cases of necrosis were discovered. — /. 
Am. M. Ass., 191 1, V. 56, pp. 1038-1039. 

Saccharin. — A widely published news note reports that the 
Secretary of Agriculture has issued a decision, based upon a finding 
of the Referee Board of Consulting Scientific Experts, which for- 
bids the use of saccharin in food on and after July i next. The 
decision is under the Food and Drugs Act and will prohibit the 
manufacture or sale in the District of Columbia or the Territories 
of foodstuffs containing saccharin, as well as interstate commerce 
in such footstuffs. 

Sanatogen. — An answer to an inquiry points out that sanatogen 
is said to contain 95 per cent, of casein so that 30 gm. (i ounce) 
of this preparation would contain approximately 28.5 gm. of protein, 
which would yield 117 calories. This is the equivalent in round 



Am. Jour. Pharm. 
June, 1911. 



Washington Branch A. Ph. A. 



295 



numbers of one-third of a pint of milk or one and one-half eggs. 
The same amount of energy would be given by an equal weight of 
starch or by one and one-fifth as much of flour or other cereals. 
The writer concludes that sanatogen like most preparations of this 
class while a food is a ruinously expensive one. — /. Am. M. Ass., 
1911, V. 56, p. 1345. 

Strophanthus. — J. Haycock outlines an assay method for 
strophanthus seeds, in which after eliminating the oil by means 
of ether, he extracts the seed with 70 per cent, alcohol and treats 
the resulting extract with sulphuric acid by means of heat to change 
the strophanthin into strophanthidin. The strophanthidin is sub- 
sequently washed out, by means of chloroform, dried at a tem- 
perature below 65° C. and weighed. The resulting yield divided 
by 0.365 gives the amount of strophanthin present. — Pharm. J., 
Lond., 191 1, V. 86, April 29, pp. 553-554- 

Xerase. — Xerase is a mixture of a specially prepared dry beer 
yeast 150 parts, grape sugar (dextrose) 20 parts, white bole 125 
parts and a mixture of nutritive salts 3 parts. Xerase is a yellowish- 
gray, powder, having a weak odor of yeast and a salty taste. It 
is only slightly soluble in water. It resists ordinary atmospheric 
conditions. — /. Am. M. Ass., 191 1, v. 56, p. 1460. 



THE CITY OF WASHINGTON BRANCH OF THE AMERI- 
CAN PHARMACEUTICAL ASSOCIATION. 

The stated meeting of the City of Washington Branch of the 
American Pharmaceutical Association for April was devoted to a 
general discussion on matters of interest to pharmacists. 

Dr. Murray Gait Motter discussed the use and advantage of a 
restricted materia medica and called attention to the efforts that 
have been and are being made in this country to bring about reforms 
in therapeutic practices. He pointed out that the need for limiting 
instruction in materia medica subjects to a restricted list of sub- 
stances is being recognized by teachers in medical schools and that 
the general trend of this tendency is well illustrated by the resolution 
adopted by teachers in the medical schools in Philadelphia at an 
informal conference called by Prof. Joseph P. Remington, on Feb- 
ruary 3, 1908. 

This resolution, in part, reads as follows : 



296 



Washington Branch A. Ph. A. 



Am. Jour. Pbarni 
.liuif, 1911. 



Resolved, That it is of the utmost importance for accuracy in 
prescribing, and in the treatment of disease, that students of medicine 
be instructed fully as to those portions of the United States Phar- 
macopoeia which are of value to the practitioner." 

To illustrate the fact that the need for restricting the materia 
medica taught in medical schools is being recognized outside of our 
own country, Dr. Motter exhibited a list of titles adopted by the 
teachers and examiners of the University of London as a basis for 
examining candidates for degrees as well as licensure. This list 
was furnished him by Dr. A. R. Cushny who, in a recent interview, 
assured Dr. Motter that unless the forthcoming edition of the 
British Pharmacopoeia was more limited in scope, and more repre- 
sentative of the best that is available in materia medica, British 
teachers of the latter subject would find it necessary to ignore the 
Pharmacopoeia entirely, and limit their teaching to the restricted 
list of medicaments mutually agreed upon. 

Dr. Motter expressed the belief that much the same conditions 
prevail in our own country, and that unless the scope of our recog- 
nized National Standards can be restricted to a reasonable number 
of articles, the books themselves must be ignored entirely by medical 
schools. He characterized the present Pharmacopoeia of the United 
States as an illustration of " would-be science," the National Formu- 
lary as " a hybrid between science and commercialism," and N. N. R. 
as " a sop to the commercial Cerberus." 

In conclusion he pointed out that in the time allotted to materia 
medica in the present medical curriculum, it is practically impos- 
sible to discuss, intelligently, more than a limited number of the 
more important medicaments and that the resolutions adopted at the 
recent conferences in Chicago, attended by representatives of various 
organizations, indicate a rather wide-spread interest in a more re- 
stricted materia medica. As an illustration of the tendency mani- 
fested, he read the following preamble and resolution adopted at 
the annual meeting of the Association of American Medical Colleges, 
held in Chicago, February 27-28, 191 1 (/. Am. M. Ass., Chicago, 
April 8, 191 1, V. 56, p. 1065). 

Whereas, The time devoted to the study of pharmacology, 
materia medica and therapeutics is necessarily limited, and 

" Whereas, The thorough knowledge of a small but representa- 
tive group of medicaments is conducive to scientific progress in 
therapeutics ; therefore, be it 



^"junrim*™"} Washington Branch A. Ph. A. 297 

" Resolved, That the Association of American Medical Colleges 
commends to the attention of medical educators and examiners, the 
Hmited materia medica lists pubhshed by the joint committee of 
the Council on Medical Education, and of the National Confederation 
of State Medical Examining and Licensing Boards, and the Chicago 
Medical Society. 

Resoh'ed, That the association urge upon the colleges and the 
examining boards the necessity for the recognition of the principle 
underlying these lists, and for the early adoption by the boards of a 
materia medica list to which licensure examinations shall largely be 
confined." 

The subject was further discussed by Messrs. Kalusowski, 
Flemer, Hilton, Hunt, and Wilbert, and the general trend of much 
of the discussion suggested the desirability of having the Pharma- 
copoeia of the United States restricted to important medicaments 
so that it might serve as the basis for materia medica instruction 
in medical schools. 

Dr. Reid Hunt expressed the belief that,^ a-: present,^ the physi- 
cian's part in the revision of the Phanracooceia is but a.-miiror .oae, 
and that much of what the better informed medical men might 
have to say is discounted by the fi'ctitious value that is ac(:'oYded to 
the reputed needs of the less conscientious, or less competent prac- 
titioner who is willing to continue the i-fse ov SLibstances that ^.p^pear 
to have no recognizable medicinal value. , , ; 

Mr. M. I. Wilbert called attention to some of the recent comments 
that have appeared on this same subject, and quoted Dr. D. L. Edsall 
who, in his address as chairman of the Section on Pharmacology and 
Therapeutics of the American Medical Association, points out that 
the Pharmacopoeia of the United States is now used by but few 
teachers of materia medica and is little known tO' medical practi- 
tioners. 

" Revision may make it better or may make it even worse so 
far as its usefulness to students and practitioners is concerned, 
according as it is intended to make it purely a reference book or 
also a practical working book ; in other words, whether it is revised 
upward or downward. 

Unless marked changes are made in it, however, it will remain 
as it is now, chiefly a name to the vast majority of the medical 
profession and will render no appreciable service in improving thera- 
peutic practice." 



298 Philadelphia College of Pharmaey. {^'^\uZ'\^i"'^' 

Mr. Samuel L. Hilton reported a series of experiments to deter- 
mine the most desirable method of procedure for making Magma of 
Magnesia N.F. He exhibited a number of samples and presented a 
formula for a preparation that contains considerably more Mag- 
nesium Hydroxide than does the one at present official. (See p. 268.) 

The Secretary exhibited a number of preparations, made by 
Mr. Otto Raubenheimer, illustrating some of the additions and 
changes embodied in the Ph. Germ. V. 

He also exhibited a number of samples of Solution of Peptonate 
of Iron with Manganese N.F., made by Mr. John K. Thum, accord- 
ing to a formula proposed for the N.F., showing the possible varia- 
tions resulting from slight modification of the method of procedure. 
Mr. Thum presents a modification of this formula, but ventures the 
opinion that the formula and method of making proposed by Dun- 
ning, in 1905, give much more satisfactory results. 

Mr. S. L. Hilton, as Secretary of the Board of Pharmacy of 
the District of Columbia, called attention to the objections that have 
been majde. to a r^icent. ruling of the board that the local dental 
supply depots, could, .^ot legally sell narcotic drugs. The subject 
yvas discussed at sp^ue. length, and on motion of Mr. Bradbury, 
seconded by Mr., fliphardson, it_ v;as agreed that the members of 
the City of Washington Branch of the American Pharmaceutical 
Association endorse, the, present efiforts of the Board of Pharmacy 
to enfo,r.ce, th,e pharmacy laws of the District of Columbia." 

M. I. WiLBERT, Secretary. 



PHILADELPHIA COLLEGE OF PHARMACY 



The ninetieth annual commencement of the Philadelphia College 
of Pharmacy was held in the American Academy of Music on 
Thursday evening, May 25. After a prayer by the Rev. Edwin S. 
Carson, the degrees were conferred by the President, Howard B. 
French. 

The following are the names of those who received the degree 
of Doctor in Pharmacy (P.D.), with the subjects of their theses: 



Name. 

Allison, James Harrison, 
Atkins, John Walt, 
Baradofsky, Samuel, 
Beckley, Norman Clyde, 



Thesis. Residence. 

Ferri Sulphas Exsiccatus, Pennsylvania 

Cacao, Pennsylvania 

Action of Iodine on Starch, Pennsylvania 

Acidum Sulphuricum Dilutuni, Pennsylvania 



Am. Jour. Pharm. 
June, 1911. 



I Philadelphia College of Pharmacy. 



Name. 
Bellitz, Miss Jennie, 
Berry, DeWilton Snow- 
den, 

Bloes, Lee Otto, 
Bollinger, Chester Eu- 
gene, 

Bradley, Kersey Elmer, 
Bradley, Oscar Samuel, 
Bricker, Robert Osborn, 
Brush, Franklin Cotton, 
Burtt, Lloyd, 
Butler, John Albert, 
Calvin, William Ray 

(P.C), 
Carey, George Warner, 
Carpenter, Pierce Ray- 
mond, 

Carrington, Arthur Hud- 
son, 

Christopher, Louis Ed- 
ward, 
Cohen, Philip, 
Costenbader, Clayton 

Elmer, 
Crawford, William 

Burton, 
Davis, Elliot Veil, 
Donnelly, John Henry, 
Edwards, David Everett, 
Eisman, David William, 
Ennis, James Henry, Jr., 
Farrell, Walter John, 
Friedman, Nathan 

Meyer, 
Gaskell, Walter James, 
Gault, Claude Ellsworth, 
Gordon, David Harris, 
Greaves, Alvah Frank, 
Greeninger, Charles 

Wenger (P.C), 
Gregory, Harrison W., 
Haimowitz, Morris, 
Hancock, Clyde Ray- 
mond, 
Hart, Farel, 
Heacock, Clifton 
Elwood, 



Thesis. 



Colocynth, 



Drug Store Management, 
Vanishing Cold Creams, 

Physiological Testing of Ointments, 
Sterilization of Cocaine Solutions, 
Ergot, 

Cultivation of Atropa Belladonna, 
Rhus Glabra, 

Determination of Stearic Acid, 
Petrox, 

Liquor Potassii Arsenitis, 
Hydrastis Canadensis, 



299 
Residence. 

Russia 

Maryland 

Pennsylvania 

Pennsylvania 

Pennsylvania 

Pennsylvania 

New Jersey 

Pennsylvania 

Pennsylvania 

Pennsylvania 

Pennsylvania 
Pennsylvania 



Ointment of Mercuric Nitrate, Pennsylvania 
Expressed Almond and Peach Kernel 

Oil, New York 

Diluted Hydrochloric Acid, Massachusetts 

Sapo Mollis, Pennsylvania 

Hydrastis Canadensis, Pennsylvania 

Mel, Pennsylvania 

Rhamnus Frangula, Pennsylvania 

Liquor Sodae Chlorinatae, Pennsylvania 

Rhamnus Purshiana, Pennsylvania 

Olive Oil, Russia 

Ether, Pennsylvania 

Fluidextract of Parsley Root, New York 

Essence of Pepsin N.F., Pennsylvania 

Elixir Digestivum Compositum, Pennsylvania 

Petrolatum, Ohio 

Bay Rum, Georgia 

Peanut Oil, New York, 
Elixir Ferri, Quininae et Strychninae 

Phosphatum, Pennsylvania 

Soft Gelatin Capsules, Pennsylvania 

Calcium Oxalate in Podophyllum, Pennsylvania 



Aletris Farinosa, 
Solidified Alcohol, 

Fluidextract of Kola, 



Pennsylvania 
Ohio 

Pennsylvania 



300 



PJiiladclphia College of Pharmacy. 



Name. 

Held, John C, Jr., 
Hemminger, Robert 
Elton, 

Hendricks, Lyle Valling- 
ton, 

Herr, Clarence Sloan, 
Hildebrand, Charles 

Pinkney, 
Hinski, Herman Leo, 
Hosfeld, Herman 

Francis. 
Johnson, David Emil, 

Kaehler, Carl Frederick, 
Kreamer, Oscar Perry, 
Lathrop, William 

Norman, 
Lemen, Hermann Light, 
Lightner, Walter Irvin, 
Longaker, Louis, 
Lowe, Edgar Walthour, 
Lynn, Ellsworth 

Waldemar, 
McNutt, William Clyde, 
Marshall, William 

Elisha, 
Martin, Joseph Stanislas, 

Martz, Samuel George 

Washington, 
Melville, Frederick 

Thornton, 
Messinger, Martin 

Lester, 
Miller, Jacob J., Jr., 

Miller, Noble Collins, 
Millrood, Samuel, 
Moore, Albert 
Worthington, 
Morley, John Edward, 
Morris, Edwin Kramer, 
Muthig, Charles, 

Myers, Louis Henry, 
Neal, Clark (P.C.), 
Oswald, Lewis William, 



Thesis, 

Milk — Its Cereal Modification, 

Show Globe Colors, 

Aqua Hydrogenii Dioxidi, 
Steel, 

Maize Oil, 
Disastase, 



J Am, Jour. Pharm. 
\ June, 1911. 

Residence. 

Pennsylvania 

Pennsylvania 

Oregon 
Ohio 

North Carolina 
Pennsylvania 



Bacillus Acidi Lactici, Ohio 

Fluidextracts of Celery and Angelica 

Root, Pennsylvania 

Sulphuric Acid, Pennsylvania 

Prescription Difficulties, Pennsylvania 

A Saponaceous Dentrifrice Elixir, Connecticut 

Acidum Hydriodicum Dilutum, Maryland 

Chloroform. Pennsylvania 

Unguentum Resorcini Compositum, Pennsylvania 

Advertising as Applied to Pharmacy, Pennsylvania 



Rhanuis Purshiana, 


Pennsylvania 


Liquor Calcis, 


Pennsylvania 


Galla, 


Pennsylvania 


Cultivation of Nicotiana Tabacum 


in 


Lancaster, County, Pa., 


Pennsylvania 


Aloes and Aloin, 


Pennsylvania 


Tobacco and Smokecraft, 


Pennsylvania 


Pilocarpus — Its Preparation and 


Action, 


Pennsylvania 


The Physician's Prescription^ — 


To 


Whom Does it Belong? 


Pennsylvania 


Medicated Waters, 


Pennsylvania 


Fluidextract of Gentian, 


Russia 


Alcohol as Sold by Retail Pharma 




cists, 


New Jersey 


Antidiphtheric Serum, 


New York 


Tinctura lodi, 


Virginia 


Sources of Salicylic Acid and It 


s 


Uses, 


New York 


Hydrastis, 


Pennsylvania 


Theobroma Cacao, 


Pennsylvania 


Glycerin, 


New York 



Am. Jour. Pharm. ) PhiJn/ 
June, 1911, ; r-nuat 

Name. 

Patterson, George 

William, Jr., 
Patton, Frank Oakman^ 
Paxson, Leon Kirk, 

Penney, Theodore 

Rufus, 
Pettit, Albert Worrell, 
Phillips, Robert Earl, 
Rachmil, Albert, 

Ralston, John Morrow, 
Rapaport, Julius George, 
Read^ Thomas Preston, 
Rice, Wallace Stoddard, 
Riley, Frank Louis, 
Rogers, Edson William, 
Rose, William Wilson, 
Rosenberg, Samuel 

(P.C.), 
Rothrock, Roswell John, 
Rovner , Israel, 
Runyan, Edwin Percy, 
Ryan, Edward Hen'-y. 
Sammons, George Israel, 
Sands, Paul Douglass, 

Sasse, Arno Richard, 
Schauermann, Howard 

George, 
Schell, Frank Wacker, 
Schmidt, Miss Selma L. 

(P.C.), 
Segal, Nathaniel Jules, 
Shaker, Elias, 

Shearer, George Key- 
worth, 
Shiles, Stanley Andrew, 
Shugars, George For- 
rester, 
Smith, Edgar Chellis, 
Smith, Robert Edgar, 
Jr., 

Snvder, Marshall 

Prescott, 
Somers, Wilbert, 



lelphia College of Pharmacy. 


301 


Thesis. 


Residence. 


Phthalic Acid, 


Pennsylvania 


Acidum Nitricum Dilutum, 


Massachusetts 


The Physical and Chemical Constants 


of Goose Fat, 


Pennsylvania 


Casein Creams, 


Oklahoma 


Tooth Washes, 


New Jersey 


Label Paste, 


Pennsylvania 


The Ethics of Harmony Between Two 


Allied Professions, 


Pennsylvania 


Syrup of Chocolate as a Vehicle, 


Pennsylvaiiia 


Strophanthus Kombe, 


Russia 


Medicine as an Economic Science, 


Pennsylvania 


Pilocarpus, 


Pennsylvania 


Fermentation, 


Maine 


Olive Oil, 


New Jersey 


Capsicum in Tincture of Ginger, 


Delaware 


Camphor Cream, 


Pennsylvania 


Fluidextract of Juniper, 


Pennsylvania 


Solution of Calcium Creosote, 


New Jersey 


Theatrical Cold Creams, 


Pennsylvania 




Pennsylvania 


Cannabis Indica, 


Pennsylvania 


The Determination of Phosphoric 


Acid, 


Pennsylvania 


Liquid Petrolatums, 


Missouri 


Glycerinum, 


Pennsylvania 


Color Standards for Galenicals, 


Pennsylvania 


The Testing of Balsam of Peru, 


Ohio 


Opium, 


Pennsylvania 


The Production of Lactic Acid 


by 


Tablets Under Differing Conditions, New York 


Goldner's Test for Cocaine, 


Pennsylvania 


Acacia and Its Uses, 


Delaware 


Trillium and Its Fluidextracts, 


Pennsylvania 


Label Paste, 


Pennsylvania 


Cactus Grandiflorus, 


Florida 


Essence of Pepsin, 


Pennsylvania 


Cologne Water, 


New Jersey 



302 



Philadelphia College of Pharmacy. 



Name. 

Southard, Paul Harri- 
man, 

Steelman, Ethelbert, 
Stein, Morris, 
Strauss, Raymond 

Albert, 
Sylvester, William 

Grimes, 
Tanner, Thomas 

Bernard, 
Temperton, Leith 

Sylvester, 
Udell, William Howard, 
Vanlnwegen, Frank P. 

(P.C.), 
Verstine, Samuel Philip, 
Watkins, Llewellyn 

James, 
Wear, John, 

Wepfer, Adolph Gustav, 
Winter, John Coleman, 
Wolford, James Scott, 
Young, Frank Aloysius, 



Thesis. 



The Glycerophosphates, 

Syrup of Hydrochlorphosphates, 

Cold Creams, 



Am. Jour. Phsrm. 
June, 1911. 

Residence. 

Ohio 

Indiana 

Pennsylvania 



Animal Diastase, 
Phenolphthalein— 
Body, 



•Its Action in the 



Ergota, 

Solution of Iron Peptonate and 
ganese, 

Cocaine and Its Legislation, 

Hamamelis Folia, 
Crystallization, 

The Dispensing Physician, 
Liquor Ferri Albuminati, 
Baptisia Tinctoria, 
Panax Quinquefolium, 
The Abuse of Narcotics, 
Cod Liver Oil, 



Man- 



Pennsylvania 

Pennsylvania 

Pennsylvania 

Pennsylvania 
Pennsylvania 

New York 
Pennsylvania 

Pennsylvania 

Pennsylvania 

Wisconsin 

Pennsylvania 

Pennsylvania 

Pennsylvania 



The following are the names of those who received the degree 
of Pharmaceutical Chemist (P.C.), together with the subjects of 
their theses : 



Name. 

Charleston, Julius Lewis, 
Duvoisin, Frank, 
Flickinger, William 

Gordon, 
Graefif, William Lewis, 
Greaves, Mrs. F. 

Hunter, 
Hartenstein, Earl 

Stewart, 
Hedges, Francis Xavier, 
Kramer, Raymond John, 
Langton, Daniel Joseph, 
Shoemaker, Clayton 

French, Jr., 



Thesis. 

A Tasteless Castor Oil, 
Carbon Tetrachloride, 

Fabrica Farinae, 
Desiccated Thyroid Glands, 

Diluted Hydrobromic Acid, 



Residence. 
Pennsylvania 
Pennsylvania 

Pennsylvania 
Pennsylvania 

North Dakota 



Liquor Ferri Chloridi, Illinois 
Tragacanth and Indian Gum, Pennsylvania 
Tinctura Ferri Chloridi, W. Virginia 

Pepsin, Pennsylvania 

Chemistry of the Vanilla Beans and 

Manufacture of the Extract, Pennsylvania 

The following were awarded certificates of proficiency in chem- 
istry : Allen, James Henry (P.D.) ; Denzler, Edward O. ; Duvoisin, 
Charles ; Haines, Frank Earl ; and Swain, J. Harry. 



^"june.^m*'*'"'} Philadelphia College of Pharmacy. 303 

The certificate in the Pure Food and Drug Course was awarded 
to Peter Amsterdam, P.P. There were 137 candidates for the 
degrees in course, coming from the various States and countries 
as follows : Connecticut, 2 ; Delaware, 2 ; Florida, i ; Georgia, 2 ; 
Indiana, i; Illinois, i; Maine, i; Maryland, 2; Massachusetts, 2; 
Missouri, I ; New Jersey, 7 ; New York, 8 ; North Carolina, i ; 
North Dakota, i; Ohio, 6; Oklahoma, i; Oregon, i; Penn- 
sylvania, 90; Russia, 4; Virginia, i; West Virginia, i, and Wis- 
consin, I. 

The address to the graduating class was made by Hon. Willis 
L. Moore who delivered an interesting discourse upon " the weather," 
discussing some of the more interesting phenomena relating to 
the physics of the atmosphere and distinguishing between hurri- 
canes, cyclones, tornados and thunder storms. 

AWARD OF PRIZES. 

The following students received the grade of distinguished : 
Pierce R. Carpenter and Herman L. Hinski. The grade of meri- 
torious was attained by John A. Butler and Morris Hiaimowitz. 

The William B. Webb Memorial Prize, a gold medal and 
certificate offered for the highest general average in the branches 
of committee, operative pharmacy and specimens, was awarded to 
Pierce R. Carpenter, the presentation being made by Mr. Walter 
A. Rumsey. The following graduates received honorable mention 
in connection therewith : Franklin Brush, John A. Butler, Charles 
P. Hildebrand, Herman L. Hinski, William E. Marshall, Edwin 
K. Morris, William W. Rose, Paul D. Sands, William G. Sylvester, 
Thomas B. Tanner, and Adolph G. Wepfer. 

The Chemistry Prize, $25, offered by Prof. Samuel P. Sadtler, 
for knowledge of chemical quantitative analysis, was awarded to 
Edwin K. Morris. The following graduates received honorable 
mention in connection therewith : Herman L. Hinski and George 
K. Shearer. 

The Materia Medica Prize, $25, offered by Prof. Clement B. 
Lowe, for the best examination in materia medica and in the 
recognition of materia medica specimens with a meritorious thesis, 
was awarded to Edwin K. Morris. The following graduates re- 
ceived honorable mention in connection therewith : James H. 
Allison, John A. Butler, Pierce R. Carpenter, Morris Haimowitz. 



304 Philadelphia CoUci^^c of Pharmacy. {'^'^tZ^'ion''"'' 

Charles P. Hildebrand, Herman L. H;inski, Samuel G. W. Martz, 
Charles Muthig, Leon K. Paxson, and Adolph G. Wepfer. 

The Microscopical Research Prize, a Zentmayer Microscope, 
offered by Prof. Henry Kraemer for the most meritorious thesis in- 
volving original microscopic work, was awarded to Julius G.^Rapaport. 
The following graduates received honorable mention in connection 
therewith: Jennie Bellitz, Kersey E. Bradley, Morris Haimowitz, 
Clyde R. Hancock, Herman F. Hosfeld, and Adolph G. Wepfer. 

The Analytical Chemistry Prize, $25, offered by Prof. 
Frank X. Moerk, for the best work in qualitative and quantitative 
analysis, was awarded to Herman L. Hinski. The following gradu- 
ates received honorable mention in connection therewith : John A. 
Butler, Pierce R. Carpenter, Walter J. Farrell, Charles P. Hilde- 
brand, and William E. Marshall. 

The Operative Pharmacy Prize, $20 in gold, offered by Prof. 
Joseph P. Remington, for the best examination in operative phar- 
macy, was awarded to Thomas B. Tanner, the presentation being 
made by Dr. E. Fullerton Cook. The following graduates received 
honorable mention in connection therewith : John W. Atkins, Norman 
C. Beckley, Franklin C. Brush, David E. Johnson, Oscar P. 
Kreamer, and Marshall P. Snyder. 

The Maisch Pharmacognosy Prize, $20 in gold, established 
by the late Jacob H. Redsecker, of Lebanon, Pa., and continued 
as a memorial by his nephew, Jacob Redsecker Beetem, for his- 
tological knowledge of drugs, was awarded to William W. Rose, 
the presentation being made by Mr. Clayton F. Shoemaker. The 
following graduates received honorable mention in connection there- 
with : Philip Cohen, Morris Haimowitz, Herman L. Hinski, Edwin 
K. Morris, and Adolph G. Wepfer. 

The Maisch Botany Prize, $20, offered by Mr. Joseph Jacobs, 
of Atlanta, Ga., for the study of native medicinal plants, was 
awarded to Adolph G. Wepfer, the presentation being made by 
Dr. Adolph W. Miller. The following graduates deserve honorable 
mention in connection therewith : Jennie Bellitz, Morris Haimowitz, 
Clyde R. Hancock. 

The Theoretical Pharmacy Prize, a Troemmer Agate Pre- 
scription Balance, established by the late Mahlon N. Kline for the 
best examination in theory and practice of pharmacy, was awarded 
to Pierce R. Carpenter, the presentation being made by Mr. C. 



^""■j^iZ^'mr"'} Philadelphia College of Pharmacy. 305 

Mahlon Kline. The following graduates received honorable mention 
in connection therewith : Samuel Baradofsky, John A. Butler. 

The Commercial Training Prize, $20 in gold, offered by 
Prof. Joseph P. Remington to the graduate who passed the best ex- 
amination in commercial training at the final examination for the 
degree, was awarded to Edwin P. Runyan, the presentation being 
made by Mr. Warren Poley. The following graduates received 
honorable mention in connection therewith : John A. Butler, Pierce 
R. Carpenter, James H. Ennis, Jr., Morris Haimowitz, Herman L. 
Hinski, Edgar W. Lowe, Frank O. Patton, Roswell J. Rothrock, 
Clayton F. Shoemaker, Jr., and Robert E. Smith. 

The Instructor's Prize, $20, offered by the Instructors of 
the College for the highest term average in the branches of phar- 
macy, chemistry, and materia medica, was awarded to Samuel G. 
W. Martz, the presentation being made by Prof. Freeman P. 
Stroup. The following graduates received honorable mention in 
connection therewith : Samuel Baradofsky, Herman L. Hinski, and 
Edwin K. Morris. 

The Pharmacy Quiz Prize, one year's membership in the 
American Pharmaceutical Association, offered by Prof. Charles 
H. LaWall for the best term work in theory and practice of 
pharmacy, was awarded to Samuel G. W. Martz. The following 
graduates received honorable mention in connection therewith : 
Samuel Baradofsky, Arthur H. Carrington, Edwin K. Morris, 
Charles Muthig, and Edwin P. Runyan. 

The Kappa Psi Fraternity Prize, a gold medal, offered by 
the Eta Chapter of the Kappa Psi Fraternity to the graduate 
making the highest general average during his or her senior year 
at the College, was awarded to Pierce R. Carpenter, the presenta- 
tion being made by Dr. George L. Htolstein. The following gradu- 
ates received honorable mention in connection therewith : John A. 
Butler, Morris Haimowitz, and Herman L. Hinski. 

The Athletic Prize, a silver loving cup, offered by Henry S. 
Godshall, P.D., and John J. Bridgeman, P.D., to the member of 
the graduating class who, at commencement, stands with the greatest 
number of points in athletics to his credit and has obtained the 
highest general average amongst those participating in athletics at 
the College, is awarded to Clyde R. Hancock, the presentation being 
made by Dr. William Schleif. The following graduates deserved 
honorable mention in connection therewith : Kersey E. Bradley, 



3o6 International Congress Applied Cheniistryi^^'^-^^^^^^'^^^^''"'- 

Robert O. Bricker, Louis E. Christopher, A. F. Greaves, Farel Hart, 
Herman F. Hosfeld, A. W. Moore, John E. Morley, Louis W. Os- 
wald, Frank O. Patton George K. Shearer, John Wear, and Frank 
A. Young-. 

In addition to those above mentioned, a special prize was 
offered this year. The will of the late George Washington Hayes 
of Lebanon, stipulated that the gold watch, which he had received 
as a member of the class of 1882. from Messrs. Allaire, Woodward 
& Co., for his work on powdered drugs, was to be awarded to the 
most distinguished student of the class of 191 1. This prize was 
awarded to Pierce R. Carpenter, the presentation being made by 
Mr. Joseph L. Lemberger. 



EIGHTH INTERNATIONAL CONGRESS OF APPLIED 

CHEMISTRY 

At the instance of the representatives of more than 4,000 
American chemists, the Congress of the United States by Joint 
Resolution on March 4, 1909, authorized the President of the 
United States to invite the Eighth International Congress to meet 
in the United States. This invitation was extended to the Seventh 
International Congress in London, June 2, 1909, by the Honorable 
Whitelaw Reid, Ambassador from the United States to Great 
Britain, and enthusiastically and unanimously accepted. 

The thirteen Delegates sent by the Government of the United 
States to the Seventh Congress were appointed by that Congress 
as the nucleus of the Organizing Committee for the Eighth 
Congress, with power to add to their number. 

On June 11, 1910, the gentlemen forming this nucleus met and 
organized for the despatch of business, and at a meeting held 
August 26, 1910, greatly increased the membership of the Organ- 
izing Committee. These Offtcial Representatives are primarily 
charged with the responsibility of seeing to it that none of the 
interests in their respective jurisdictions are overlooked at the 
Eighth Congress, and that all are properly represented thereat ; 
they also serve as an ofiBcial avenue of communication between 
their respective Governments and the Eighth Congress. This en- 
larged Organizing Committee, on October 8, 19 10, provided for 



jllne^m*^™' } ^^'it^^^^ational Congress Applied Chemistry. 307 

a Constitution and By-Laws, and further provided for 25 scientific 
Sections and Subsections. One of these — on the leather industries 
— still remains to be organized if those interested in leather and 
allied manufactures desire to have a special Subsection in the 
Eighth Congress. Sectional Executive Committees for each of the 

24 Sections and Subsections have been organized. The task of 
completing the working committees (comprising a total of about 

25 members each) for all of these 24 Sections and Subsections is 
going rapidly forward. 

The responsibility for the conduct of the Eighth Congress is 
vested in the Executive Committee. 

The responsibility for the conduct of business before the various 
Sections and Subsections at their sessions during the Congress is 
vested in a Committee on Sectional Procedure, which Committee 
is composed of all the Presidents of Sections and Subsections, and 
tentative rules have been framed. 

The Committees of Sections and Subsections, and particularly 
their respective Executive Committees, are charged with the re- 
sponsibility of procuring papers for all their sessions, not only 
from chemists and others resident in the United States, but also 
from those resident in all other countries of the world. To the 
end that the most effective co-operation may be secured, it is 
earnestly urged that, in all countries outside the United States, 
there be very soon formed Committees of Sections and Subsections 
corresponding to those established in the United States, or so 
many of them as will provide fully for the interests of chemists 
and allied professional and business men in such countries as ma 
not be interested in all the Sections and Subsections of the Eighth 
Congress, and that, upon organization and announcement of such 
Committees, all chemists and all chemical and allied societies resi- 
dent in such country and interested in the Eighth Congress com- 
municate with those of their Committees in whose activities and 
purposes they are interested, giving the titles and scope of papers 
or other communications they may contemplate contributing to the 
Eighth Congress. It is suggested that all such societies within 
or outside .the United States, which desire to co-operate with any 
particular Section or Subsection of the Congress, communicate 
that fact to the President of the corresponding American Sectional 
Comlmittees. It is further suggested that Chairmen of Committees 
of all Sections and Subsections outside the United States com- 



3o8 International Congress Applied C7it'////^/r3;{^'",;/,';;f'jy\'i'*'™ 

municate, at stated intervals, preferably the first of every month, 
to the President of the American Committees of the corresponding- 
Sections or Subsections, the titles of papers or other communica- 
tions promised, together with the names and post office addresses 
of, tlieir authors, so that the American Committee may be able to 
form an approximate estimate of the probable activities of the 
respective Sections for the guidance of those responsible for the 
conduct of the Eighth Congress. 

In order that there may be beneficial co-operation and a close 
affiliation between the Eighth Congress and its Sections and Sub- 
sections on the one hand and other scientific or professional bodies 
meeting in or near New York or Washington at or about the time 
of the convening of the Eighth Congress, on the other, a Committee 
on Co-operation has been established; this Committee will be glad 
to communicate with any such associations in an endeavor to 
bring about such co-operation. 

The President of the United States has shown his deep interest 
in the objects and purposes of the Eighth Congress by consenting 
not only to act as its Patron, but also to preside at the Opening 
Meeting of the Eighth Congress, which is to be held in Washington, 
D. C, on Wednesday, September 4, 19 12. The President of the 
United States has also shown his great solicitude for the success 
of the Eighth Congress by causing invitations tO' be sent to all the 
Governments of the World to take part in the deliberations and 
the work of the Congress. The chemists, individually, and col- 
lectively as Societies, not only of the United States, but of all other 
countries of the world, therefore owe it not only to their science 
and to their profession to exert every effort to make the Eighth 
International Congress of Applied Chemistry completely successful, 
but they also owe it to their own countries and their own Gov- 
ernments to use every means in their power to see to it that every 
interest in their respective countries is properly and fully repre- 
sented at the Eighth Congress and to demonstrate to their own 
Governments and their fellow-countrymen that, in accepting this 
invitation of the President of the United States, the confidence 
reposed in the chemists of the respective countries by their Gov- 
ernments has been fully justified. To this end the hearty and 
enthusiastic co-operation of chemists and allied professional and 
business men, and particularly of societies of chemists, and of allied 
professional and business societies the world over, and along the 




'•^International Congress Applied Chemistry. 



309 



lines suggested at various places in this pamphlet, is most earnestly 
solicited. 

It is hoped that all the matters relating to- this Congress will be 
given the widest possible publicity in all chemical and allied so- 
cieties, and in all chemical and allied publications the world over, 
and that suggestions for changes which may more surely assist in 
the realization of a successful and profitable meeting may be made 
to the Executive Committee of the Eighth Congress. 



Eighth International Congress of Applied Chemistry. 



New York, March 6th, 191 1. 

TENTATIVE RULES GOVERNING THE RECEIPT OF 
PAPERS FOR PRESENTATION OR PUBLICATION 

1. All papers should be in the hands of the American Comimittee 
on or before July i, 191 2. 

2. All such papers should be presented in duplicate, legibly 
written, but preferably typewritten. 

3. Each paper must be accompanied by an abstract thereof, 
also in duplicate, legibly written, but preferably typewritten. 

4. All papers received prior to July i, 1912, and accepted for 
publication will be printed prior to the meeting of the Congress 
and grouped according to the Sections to which they are assigned ; 
papers received after July i, 19 12, and accepted for publication 
will be printed prior to the meeting of the Congress if practicable, 
but it cannot be guaranteed that they will be placed in the Section 
to which they belong, but they may appear in an appendix. 

5. The American Committee will neither revise nor edit any 
papers or abstracts ; papers received for publication will be printed 
in extenso as ofifered, or only the abstract accompanying the full 
paper will be printed, or the paper will be printed by title only, 
together with the name and post office address of its author, or 
the paper will not be ])rinte(l at all, as may be decided in each case 
by the Committee on Papers and Publications. 



Respectfully, 



Edward W. Morley, 

Honorary President. 



William H. Nichols, 
President. 



Bernhard C. Hesse, 
Secretary. 



310 International Congress Applied CJieiiiistry^j^^^'^^^l^^Ai]^^^.^^ 

6. Authors will not receive printer's proofs of papers or ab- 
stracts submitted ; authors must do their proofreading on the 
manuscript ; whatever is printed by the American Committee will 
be printed in exact accordance with whichever of the authors' 
manuscripts is selected for publication. 

7. Discussions will be recorded in the official language in which 
they are uttered, and participants in the discussions will have an 
opportunity of editing the manuscript report of such discussion ; 
the American Committees will print from such edited manuscript 
report of the discussion, and printer's proofs will not be sent to 
participants. 

8. No paper which has previously been published shall be read 
at the Eighth Congress nor printed in its final Report without the 
consent of the Sectional Executive Committee, the Committee on 
Papers and Publications and the Executive Committees of the Eighth 
Congress having first been obtained. 

Note : The American Committee will proceed to print the 
papers during the first half of July of 191 2. The size of the 
edition printed will be determined by the number of membership 
fees received on or before July i, 1912; persons contemplating 
membership in the Congress should have their membership com- 
pleted prior to July i, 1912, in order that they may be sure of 
receiving a copy of the Report of the Congress ; membership 
fees can be received after July i, 191 2, only as subject to the 
condition that copies of the Report of the Congress cannot be 
guaranteed, and will be supplied only until the number of extra 
copies printed shall have been exhausted. 

Merck's Manual of the Materia Medica. (Fourth Edition.) A Ready 
Reference Pocket Book for the Physician and Surgeon. Containing a compre- 
hensive list of Chemicals and Drugs — not confined to " Merck's " — with their 
synonyms, solubilities, physiological effects, therapeutic uses, doses, incom- 
patibles, antidotes, etc. ; a table of Therapeutic Indications, with interspersed 
paragraphs on Bedside Diagnosis, and a collection of Prescription Formulas, 
beginning under the indication " Abortion " and ending with " Yellow Fever " ; 
a Classification of Medicaments ; and Miscellany, comprising Poisoning and 
Its Treatment ; and an extensive Dose Table ; a chapter on Urinalysis, and 
various tables, etc. (Merck & Co., 45 Park Place, New York, 1911. 493 
pages. While compiled for the use of physicians, there is much in the book 
regarding the materia medica, doses, urinalysis, etc., to make it a serviceable 
reference work for pharmacists also. Sent on receipt of forwarding charges 
of 10 cents, in stamps, to pharmacists, or to students enrolled in any College 
of Pharmacy, in the United States.) 



THE AMEEIOAN 

JOURNAL OF PHARMACY 

JULY, igii 

VOLUMETRIC DETERMINATION OF MERCURY. 

By Carl E. Smith. 
Laboratory of the Powers-Weightman-Rosengarten Co., Philadelphia. 

Abstracts oi a Report by a Committee of the Division of Pharma- 
ceutical Chemistry of the American Chemical Society have appeared 
in recent journals (see this Journal, 191 i, v. 83, p. 186), the work 
reported on being a comparison of various methods for the deter- 
mination of mercury in the medicinal compounds of this metal. 

The purpose of these notes is to relate some recent experiences 
with two of these methods, which are probably the simplest and most 
reliable of those mentioned in the report, the Hempel method for 
mercurous and the Rupp method for mercuric compounds. It is 
desired also to call attention tO' one other, which is perhaps the best 
volumetric method available for some purposes. 

The writer's experience with the Hempel method, in its appli- 
cation to calomel and mercurous iodide, corroborates to a consider- 
able extent the results of the committee. The objectionable feature 
of it, noted by several of the members, that long-continued shaking 
is needed to bring the salt into solution, may be eliminated, it was 
found, by the simple change of adding the iodine solution first, in- 
stead of the potassium iodide. When this is done and the mixture 
at once shaken vigorously in a stoppered flask, solution is effected 
very quickly. The final result is the same in either case, as com- 
parative trials have shown. It seems advisable, also, to increase 
the quantity of sam])le, to lessen the experimental error, in the case 
of calomel to about i Cim. The most satisfactory results were 
obtained when working in the following manner: To about i Gm. of 
calomel, accurately weighed, contained in a glass-stoppered 300 c.c. 

(311) 



312 Volumetric Determination of Mercury. {^^'/X^iu'^^' 

Erlenmeyer flask, add 50 c.c. of n/io iodine solution. Mix by 
rotating until the salt is thoroughly moistened, then add a solution 
of 2 Gm. of potassium iodide in 10 c.c. of water and at once shake 
the stoppered flask vigorously until solution is complete. Titrate 
the excess of iodine with n/io sodium thiosulphate, using starch 
solution as indicator, adding the latter when the liquid is nearly 
decolorized. Each c.c. of n/io iodine solution consumed corre- 
sponds to 0.02355 Gm. of mercurous chloride. 

A sample of calomel, practically chemically pure, assayed by this 
method 99.5 to 100.0 per cent., the average of 6 determinations being 
99.7 per cent., with some variation in the working details. Prac- 
tically the same figures were obtained with yellow mercurous iodide 
containing slight traces of impurities. 

The criticism of the Rupp method, that reduction of the mercury 
is not complete within a reasonable time without the use of heat 
and that, when heat is employed, the mercury is not easily dissolved 
afterwards, is well founded, if Rupp's directions in outhning the 
method (Berichte d. d. ch. Ges., 1906, v. 39, p. 3702), be taken 
literally as regards the quantity of alkali to be used. While his 
directions lead to the inference that only enough is required to com- 
bine with the acids formed by the reaction, his figures in the same 
paper show that he used a decided excess, not less than 10 c.c. of 
normal solution for 0.2 Gm. of mercuric chloride. The divergent 
opinions regarding this method by the members of the committee 
are doubtless due chiefly to differences in the quantities of alkali 
used. When the above mentioned proportions are taken, the reac- 
tion is almost instantaneous, unless the solution is excessively 
diluted, and may safely be regarded as complete within 5 minutes, 
without heating. It will do no harm to use a still larger excess of 
alkali or to let the mixture stand longer. Shaken in a stoppered 
flask with the iodine solution, the precipitate is then dissolved very 
readily. A large excess of acetic acid is to be avoided, as it tends 
to make the result too low, which is also the experience of Mr. L. D. 
Havenhill, of the committee. The best results were obtained by 
carrying out the details as follows : Dissolve about 0.5 Gm. of 
powdered mercuric chloride, accurately weighed, contained in a 
glass-stoppered 300 c.c. Erlenmeyer flask, in a solution of 2 Gm. of 
potassium iodide in 10 c.c. of water. Add 25 c.c. of normal caustic 
alkali solution and 6 c.c. of 40 per cent, formaldehyde solution. 
Mix by swirling the flask occasionally during 10 minutes, then acidu- 



^"■j^uy^m*'^"'' } Volumetric Determination of Mercury. 313 

late with about 5 c.c. of 36 per cent, acetic acid. Add 50 c.c. of 
n/io iodine solution and shake vigorously in the stoppered flask 
until the mercury is dissolved. Titrate the excess of iodine with 
n/io sodium thiosulphate solution, adding starch solution when the 
liquid is nearly decolorized. Each c.c. of n/io iodine solution cor- 
responds to 0.01355 Gm. of mercuric chloride. 

Chemically pure mercuric chloride gave by this method 99.8 to 
100.3 P^r cent., with an average of 100. i per cent, in 5 determina- 
tions. Similar results were obtained with mercuric iodide, oxide, 
ammoniated mercury, and mixtures of mercuric chloride and am- 
monium chloride colored with aniline dyes. It is the official method 
of the German Pharmacopoeia, 5th revision, 1910, for the assay of 
mercuric chloride tablets and ointment of ammoniated mercury. 

The third method alluded to above consists in the titration of 
mercuric compounds, in nitric acid solution, with sulphocyanate in 
exactly the same way as the titration of silver. It is not applicable 
in presence of chlorides and probably not in presence of other 
halogens. It was first made serviceable for accurate work by 
R. Cohn {Ber. d. d. chem. Ges., 1901, v. 34, p. 3502) and simplified 
by Rupp and Kraus (Ibid., 1902, v. 35, p. 2015). For illustrations 
of its application see below. The writer has no personal experience 
with this method, but his associates have found it accurate and use- 
ful for the assay of technical mercuric oxide containing iron. The 
German Pharmacopoeia uses it for the assay of several galenical 
preparations. For the convenience of any readers of this Journal 
interested in this subject, who may not have access to this book, 
the assay methods for mercury preparations prescribed therein are 
given here : 

Mercuric Chloride Tablets. — Composed of equal parts of mer- 
curic chloride and sodium chloride, colored with aniline dye. Dis- 
solve 2 tablets of about i Gm. each, accurately weighed, in water 
and dilute to 100 c.c. In 20 c.c. of the solution dissolve i Gm. of 
potassium iodide, add 10 c.c. of a 15 per cent, solution of potassium 
hydrate and 3 c.c. of a 40 per cent, solution of formaldehyde with 
10 c.c. of water. After one minute add 25 c.c. of 30 per cent, acetic 
acid, 25 c.c. of n/io iodine solution, and shake until the mercury is 
dissolved. Titrate the excess of iodine with n/io sodium thio- 
sulphate solution, using starch solution as indicator. Each c.c. of 
n/io iodine solution consumed corresponds to 0.01355 Gm. of 
mercuric chloride. 



314 Vohimctric Dctcrmiuafion of Mercury. 

Ointinciit of Aininoniated Mercury. — Consists of lo per cent, of 
ammoniated mercury and white vaseline. Heat about 5 Gm. of 
the ointment, accurately weighed, in a small flask with 25 c.c. of 12.5 
per cent, hydrochloric acid on a water bath. Mix frequently by 
rotating the flask during 10 minutes. Pour the acid liquid into a 
100 c.c. flask, rinse the vaseline and flask repeatedly with water and 
dilute the combined liquid and washings to 100 c.c. Transfer 25 c.c. 
to a glass-stoppered flask, add i Gm. of potassium iodide and pro- 
ceed further as directed for the assay of mercuric chloride tablets. 
Each c.c. of n/io iodine solution consumed corresponds to 0.01257 
Gm., approximately, of ammoniated mercury. 

Mercuric Salicylate. — Contains about 55 per cent, of mercury. 
Dissolve about 0.3 Gm. of the salt, accurately weighed, in dilute 
sodium hydrate solution, acidulate with acetic acid, and add 25 c.c. 
of n/io iodine solution. Let the mixture stand in a closed flask 
for 3 hours at room temperature, rotating it occasionally. Titrate 
the excess of iodine with n/io sodium thiosulphate solution. Each 
c.c. of n/io iodine solution consumed corresponds to 0.0100 Gm. of 
mercury. 

Mercury Plaster. — Contains 20 per cent, of mercury ; made with 
lead plaster, wool fat and yellow wax. Heat about 3 Gm. of the 
plaster mass, accurately weighed, with 20 c.c. of nitric acid, sp. gr. 
1.38 to 1.40, in a flask having a wide neck and connected with a 
reflux condenser. Heat about 10 minutes or until mercury globules 
are no longer visible in the sandy deposit of lead nitrate, add 25 c.c. 
of water and heat again until the fat has separated, leaving the 
aqueous layer clear. Cool and pour the solution through a tuft 
of absorbent cotton into a 100 c.c. flask. Break up the disk of fat, 
rinse it and the flask with 4 or 5 portions of 5 c.c. each of water and 
to the combined liquids add potassium permanganate until perma- 
nently red or until brown flakes separate. Decolorize or clarify the 
solution by addition of ferrous sulphate solution and dilute to 100 c.c. 
To 25 c.c. of the solution add 2 c.c. of a 10 per cent, solution of 
ferric alum and titrate with n/to ammonium sulphocyanate. Each 
c.c. consumed corresponds to o. 01000 Gm. of mercury. 

Mercury Ointment. — Contains 30 per cent, of mercury ; made 
with wool fat, peanut oil, lard, and mutton tallow. Proceed as 
directed for the assay of mercury plaster, using about 2 Gm. of the 
ointment and 20 c.c. of nitric acid. 



Am. Jour. Pliarm. ) 
July, 1911. i 



Pharmacognosy of Echinacea. 



315 



Ointment of Red Mercuric Oxide. — Contains 10 per cent, of mer- 
curic oxide ; made with white vaseHne. Proceed as directed for the 
assay of mercury plaster, using about 5 Gm. of the ointment and 
20 c.c. of nitric acid. Continue heating- until the red color of the 
mercuric oxide has disappeared. Each c.c. of n/io ammonium 
sulphocyanate solution corresponds to 0.0108 Gm. of mercuric oxide. 

The factors given throughout these notes are based on the 
atomic weights having = i6 as the standard. If the volumetric 
solutions used are made by the H = i standard, either the factors 
or the final results should be multiplied by 0.992. 



THE PHARMACOGNOSY OF ECHINACEA.^ 

By Henry Kraemer and Maud Sollenberger. 

The root of Echinacea angiistifolra has been used in certain pro- 
prietary medicines for a number of years. It was not until about 
1886, however, that the identity of the drug was determined. From 
specimens of the entire plant which were sent John Uri Lloyd from 
Nebraska, his brother C. G. Lloyd was enabled to identify the drug 
as being- derived from Echinacea angnstifolia, or the " Nigger 
Head " of the West.^ Apparently considerable quantities of the 
drug are used, and there are a number of reports to the effect 
that it is more or less adulterated. It should be stated that while 
the drug is largely used, the Council on Pharmacy and Chemistry 
of the American Medical Association-^ has investigated the subject 
and come to the conclusion that " Echinacea is deemed unworthy 
of further consideration until more reliable evidence is presented 
in its favor." However, the plant and drug have a number of in- 
teresting anatomical features, and it was deemed advisable to present 
the results of this study at this time. Authentic specimens of the 
crude drug were secured from Professor Lloyd. Living plants of 
Echinacea angnstifolia were purchased from Mr. John Hellerman, 
who has been cultivating the plant in Philadelphia, and these plants 

^ Read at the New Jersey Pharmaceutical Association meeting, June 14, 
1911. 

^ Pharm. Rcjieiv, 1904 (vol. 22), p. 11. 
Jour. A. M. A., Nov. 27, 1909; Report A. M. A. Council on Pharmacy 
and Chemistry, 1909, p. 144. 



3i6 



Pharmacognosy of Echinacea. 



Am. Jour. Pharm. 
July, 1911. 



have been growing- for some time in the garden of the Philadelphia 
College of Pharmac}^ and their identity established. 

There are two species of Echinacea which are indigenous to the 
United States. These are known by botanists under the generic 
name of Braiincria, although Hoffmann, in the monograph of the 
Compositae in Engler and Prantl's Pflanzenfamilien, still retains them 
under the genus, Rudheckia. Thus we have the following botanical 
synonyms of the species that concerns us : 

Rudheckia pallida, Nuttall (1834). 

Echinacea angustifolia, DeCa-ndoWe (1856). 

Brauneria pallida (Nuttall), Britton (1904). 

DESCRIPTION OF THE PLANT. 

Brauneria pallida is a perrenial herb, somewhat resembling 
Brauneria purpurea, a plant that is quite extensively cultivated in 
the gardens, and known as the Cone flower." The vertical rhi- 
zome and root of Brauneria pallida is, however, very much larger 
than those of the cone flower. The plant is from 3 decimetres to 
I metre high, the leaves are usually more or less crowded near the 
base of the stem, and from among them arises a long peduncled 
head of flowers. The leaves are for the most part rather narrow 
and lanceolate, pointed at both the apex and base, and with a very 
long petiole, the latter frequently being as long as the lamina. 
They are nearly entire, and with three prominent parallel veins. 
The flower heads are made up of both tubular and ray florets, the 
entire cluster being about 9 centimetres in diameter. The receptacle 
is conical and solid, and subtended by three series of imbricated 
bracts which are lanceolate, spinose, with an acute or acuminate 
apex, and appressed or slightly spreading. On the receptacle are 
borne numerous purplish tubular flowers, which are about i centi- 
metre long and partly enclosed in a somewhat woody bract with a 
narrow attenuated apex which projects several millimetres above the 
flowers. The tubular flowers are perfect, the calyx being short and 
acute, the corolla tubular and the stigmas ellipsoidal. The achenes 
are obpyramidal and with a pappus, forming a short dentate crown. 
The ray flowers are of a purplish or rose color, narrow elliptical 
or linear, about 7 centimetres long, and with two or three acute 
teeth at the apex. The ray flowers appear to be neutral, and in 
addition to the spatulate corolla, possess a short calyx tube with 
five acute, rather short, serrate teeth. 



^"'j'i^y'^im*'^™"} Pharmacognosy of Echinacea. 317 

DESCRIPTION OF RHIZOME AND ROOT. 

The crown of the rhizome is simple or branched, resembhng that 
of other Compositse. The undergroinid stem, or rhizome, attains a 
length of as much as 12 centimetres, and is from 10 to 15 milli- 
metres in diameter. It is slightly annulate, marked by a number of 
V-shaped stem scars and circular root scars, but otherwise it is 
nearly smooth and of a somewhat purplish-brown color. The root 
is continuous with the rhizome and extends downward, producing 
a number of irregular branches. 

The commercial drug may be described as follows : Nearly entire, 
cylindrical, very slightly tapering, 10 to 20 centimetres long, 4 to 
8 millimetres in diameter ; externally, grayish brown, light brown or 
purplish brown, slightly annulate in the upper portion, with occa- 
sional V-shaped stem scars, somewhat wrinkled longitudinally, or 
furrowed and sometimes slightly spirally twisted ; fracture short, 
fibrous ; internally, bark less than i millimetre in thickness, wood 
thick and composed of alternate light yellowish and black wedges ; 
the rhizome with a circular pith ; odor faint, aromatic ; taste sweet- 
ish, followed by an acrid and tingling sensation resembling that of 
aconite but lacking the persistency and numbing qualities of the 
latter. 

MICROSCOPICAL STRUCTURE. 

The outer portion of the rhizome and root (Fig. i) consists of 
two to four layers of more or less tabular cork cells with somewhat 
thickened yellowish suberized walls, the cells being frequently filled 
with more or less spherical globules of a substance which may 
become changed to a granular form. Beneath these outer layers 
of cork occur six to eight rows of tangentially elongated cells with 
more or less thickened walls, which are usually rich in cytoplasm, 
and in which is frequently found a distinct nucleus. In among 
these cells also occur some intercellular (schizogenous) oil and 
resin cavities or reservoirs (Figs, i, 4 and 5). Beneath this second 
layer occur from twelve to twenty rows of parenchyma cells of vary- 
ing shape, among which are large intercellular oil reservoirs and 
numerous small stone cells (Figs, i, 2 and 3). These stone cells 
are usually more or less elongated, and frequently ten to twenty 
times as long as they are wide. They are of considerable interest 
by reason of the fact that in the intercellular spaces and in some 
of the adjoining cells, occur blackish, carbon-like, resinous masses 



3i8 Phannacogjiosy of Echinacea. r Am. jour. Phann. 



July, 1911. 



Fig. I. 




Echinacea; A, cross section of outer layers of root, showing cork (c) and hypodermis (h) , 
S, cross section of cortex showing parenchyma (p), sphere crystals of inulin (i), and stone 
or sclerotic cells, and oleoresin reservoirs or canals (o). C, cross section of portion of fibro- 
vascular bundle showing leptome or sieve (/), cambium, (m), trachea or vessels (i) , oleoresin 
reservoirs (o), stone cells {s), parenchyma {p) and inulin crystals (i) . Z), cross section near 
endodermis showing endodermal cells with suberized radial walls or Casparyan spots (e), endo- 
dermal resin canal (o), and parenchyma (p). E, cross section of underground stem or rhizome 
showing a group of bast fibres (fe), leptome or sieve (/), and parenchyma {p) . F, a sclerotic or 
stone cell. G, parenchyma with sphere crystals of inulin adhering to the walls. H, longitudi- 
nal section showing various forms of trachea or vessels; d, double spiral; a, annular; r, with 
simple pores; p, adjoining parenchyma. 



Am. Jour. Pharm. 
July, 1911. 



I Pharmacognosy of Echinacea. 



319 



which will be referred to in some detail later (Figs. 2 and 3). In 
the rhizome there is also included in this layer somewhat irregular 
tangentially elongated groups of bast fibres (Fig. i, E), which give 
a strong reaction for lignin with phloroglucin. The walls of these 
fibres are not only lignified but are frequently very thick and almost 
transparent, very finely laminated and marked with a few simple 



Fig. 




Stone cells showing the distribution of the black intercellular substance. 

pores, which are more apparent when any of the ordinary reagents 
are employed. 

The leptome or sieve extends in rays of varying width from the 
cambium to the outer bark, being bounded in the case of the rhizome 
by the bast fibres. In between these radial rows of sieve the tissue 
for the most part is parenchymatic and contains considerable inulin. 



320 



Pharmacognosy of Echinacea. 



Am. Jour. Pharm. 
July, 1911. 



and the cells are interspersed with groups of from one to three of 
the characteristic stone cells already referred to, the groups being 
somewhat circularly disposed. The cambium zone is distinct, con- 

FlG. 3. 




Cross and longitudinarsections showing the different forms of stone cells. 



sisting of several rows of thin-walled cells. The xylem occurs in 
rays made up of small interrupted groups of tracheae which are 
separated by wood parenchyma. The tracheae are from eight to ten 
times as long as they are wide, the walls for the most part being 



^"■j'i'iy'^im*'^"''} Pharmacognosy of Echinacea. 321 

marked with simple slit-like pores, although annular and reticulate 
markings also occur. In between the xylem rays occur broad 
wedges consisting of from ten to twenty radial rows of parenchyma 
cells that are not of the type of medullary rays. Scattered among 
these cells are intercellular oil and resin reservoirs and more or 
less elongated stone cells similar to those already referred to. In 

Fig. 4. 



Cross section of root showing a large oleoresin canal (o) , tracheae or vessels (/) , and parenchyma {p) . 



the xylem rays true wood fibres are also associated with the tracheoe 
in certain specimens collected in Tennessee and Missouri. The 
wood fibres are readily distinguished from the stone cells by reason 
of their position, more uniform outline and attenuated ends. In 
very young roots, in which the primary structure is still unchanged, 
the fibrovascular strand is of the triarch type. 



322 



PJiarmacoj^nosy of Echinacea. 



Am. .lonr. Pharm- 
.liily, I'.ni. 



Fig. 5. 




Section showing development of oleoresin canals or reservoirs (a, 6, c, d and e); o, oleo- 
resin canals; p, parenchyma. F, longitudinal section showing an elongated secretory cell 
between the rows of parenchyma in the cortex. 



INTERCELLULAR SUBSTANCE. 

The Compositse are usually divided for certain anatomic/al 
reasons, as well as for morphological differences, into two principal 
groups. In the one, viz., the Tubuliflorae, occur oils and resins, 
either in intercellular canals or secretory cavities. In the other, 



'^'"■ju'iy^mi**^™"} Pharmacognosy of Echinacea. 323 

namely, the Ligiiliflorse, the oils and resins are replaced by laticifer- 
ous tubes or vessels. In only one genus (Gimdelia) of the Tubuli- 
florse are laticiferous tubes present, and while the root of this plant 
apparently contains resin canals, these are wanting in the leaves and 
stems. Again, in only one genus {Scolyinus) of the Liguliflorse are 
oil canals present, as well as latex tubes (see DeBary, p. 137; and 
Engler and Prantl, p. 351). 

The oleoresinous canals or reservoirs (Figs, i, 4 and 5) found 
in Brauneria pallida^ are of the general type occurring in the Tubuli- 
florae. They are quite numerous and in some instances quite large, 
and are found in both the wood and the bark. The contents are of 
a light yellowish, amber-like color and of an oily or resinous 
consistence. There appears to be no relationship between the sub- 
stance found in these oleo-resinous canals and the black substance 
present in most of the intercellular areas around the stone-cells. 
This latter substance is of a nearly uniform black color, insoluble 
in both sulphuric and nitric acids, and the ordinary solvents, such as 
alcohol, acetone and petroleum ether, etc. In longitudinal section, 
or upon treating the drug with Schultze's Macerating Fluid, it is 
found that this substance forms a somewhat coarse network, the 
material from a number of intercellular areas being more or less con- 
nected and the network resembling a septate latex tissue. Beyond 
this appearance there is no resemblance between the network of black 
intercellular substance and true laticiferous tissue. In some of the 
parenchyma cells of both the bark and the wood there may occur 
a black substance resembling this intercellular substance, which 
would seem to be in the nature of an excretion from some of these 
cells. 

It should be stated, however, that in some of the longitudinal 
sections there was observed in the cortical tissue a number of elon- 
gated areas containing an emulsion of a yellowish oily or resinous 
substance. It could not be determined with certainty whether these 
were in the nature of elongated secretory cells or merely inter- 
cellular spaces into which had been secreted the oleo-resinous mate- 
rial. There are a number of facts which would seem to lead to the 
inference that they are probably in the nature of elongated secretory 
cells. 

Some time ago Moscr published an article on Echinacea and a 
Spurious Root, that appeared in the fall of 1909 (AJ.Ph., iQio, 
p. 224). As he did not have an opportunity of studying authentic 



324 Fluid Extract of Echinacea. {^'''.uUV'iyu''''"'' 

material, or that derived from plants which were identified, his 
statements and description will need to be modified in order to 
accord with the facts here presented. Furthermore, the spurious 
drug described by him was really that of authentic material, as 1 
have several specimens of the root from herbarium material of 
Brauncria pallida collected in Missouri and Tennessee, which , are 
similar to the drug- examined by him. Of course it is quite likely 
that other species of Rudheckia or Braimeria, may have some of the 
fundamental characteristics of Brauncria pallida, the root of which 
together with the underground stem or rhizome, is the source of 
the drug known as Echinacea. 



FLUID EXTRACT OF ECHINACEA.^ 
By George M. Beringer. 

Echinacea is one of the vegetable drugs that, in recent years, 
has attracted considerable attention in the medical profession, and 
appears to merit more extended study. By some its virtues are 
highly extolled, by others it is considered worthless. It is, however, 
to be noted that the condemnation is largely based upon the fact 
that certain chemists who made an examination of the drug had 
failed to isolate the active principle. We need not be surprised 
at this as the chemistry of many of the compositse has been but 
little studied and very few alkaloidal or glucosidal principles have 
been isolated from drugs of this plant family. 

The aromatic principles present in Echinacea are probably the 
source of its therapeutic action. The root has a characteristic aro- 
matic, sharp and pungent taste, reminding one of the peculiar pun- 
gency of certain umbelliferous drugs such as lovage and angelica. 
It leaves a warm and tingling sensation in the mouth and is suffi- 
ciently irritant to produce a prickling sensation and a slight blister- 
ing effect on the mucous surfaces of the lips. This pungency and 
blistering effect is even more marked in alcoholic or hydro-alcoholic 
extracts. 

Echinacea is a plant indigenous to the western plains of the 
United States. The professional use was preceded many years by 

^ Read before the New Jersey Pharmaceutical Association at Asbu*- 
Park, N. J., June 14, 191 1. 



Am. Jour, Phartli. \ 
July, 1911. / 



Fluid Extract of Echinacea. 



that of certain aboriginal tribes. The Sioux Indians are said to have 
used it as a remedy in snake bites, insect stings, and in the healing 
of wounds. Its use in medical practice, to-day, is very much along 
the same lines. It is considered as a mild counter-irritant, stimulant 
and antiseptic, and as a remedy useful in blood disorders, typhus and 
meningitis and likewise recommended externally in the treatment 
of carbuncles, haemorrhoids, wounds and impotency. 

The fluid extract is the form in which the drug is commonly 
exhibited and its use certainly merits recognition and the fixing of 
an oflicial standard therefor. It is proposed to introduce a formula 
for the fluid extract in the National Formulary. In connection with 
the work of revision of this legal authority, the writer has experi- 
mented with various formulas suggested for this preparation. 

The views of manufacturers consulted showed a wide variation. 
While one recommended diluted alcohol for the menstruum another 
preferred 80 per cent, alcohol, and the recommendations of others 
fell between these extremes. This difference in the opinions ot 
manufacturers accounts for the difference existing in the commercial 
products and shows the necessity for an oflicial standard. 

My experiments lead me to the conclusion that a menstruum 
weaker in alcohol than alcohol 2 volumes, water i volume, will not 
extract the drug. A menstruum of that strength appears to make 
a fluid extract of good body and color and taste, but it is not quite 
clear and some separation takes place. A menstruum of alcohol 
3 volumes, water i volume, is a decided improvement over the 
weaker alcohol and shows only a very slight tendency to separation. 
The best result in my judgment is obtained with a menstruum of 
alcohol 4 volumes, water i volume, and is recommended for this 
fluid extract. To increase the alcohol beyond this strength seems 
unnecessary and yields a product lacking in body and no more 
aromatic than the menstruum preferred. 



326 Fifth Revision German Pharmacopoeia. {'^'"■jiHv'i.iu'""'* 

THE FIFTH REVISION OF THE GERMAN PHARMA- 

COFCEIA/ 

By George M. Beringer. 

The appearance of a new edition of the German Fhannacopoeia 
is always an important event in the history of pharmacy. The fifth 
revision of the Deutsches Arzneihnch has been pubhshed (Un-ing the 
past year and became effective and the anthority in the German 
Empire on January i, 191 1. Its pubHcation on the eve of the Ninth 
Revision of the United States Pharmacopoeia, adds materially to its 
importance. 

Owing to the great number of our inhabitants who are of Ger- 
man birth or descent and alsO' to the numerous American physicians 
who have been students in the German medical schools, the practice 
of medicine and pharmacy in this country, in many matters, largely 
follows the German. 

The present revision marks the progress of professional phar- 
macy in Germany since 1900, when the fourth revision was pub- 
lished. Many of its departures are meritorious advances and will 
have marked influence on other pharmacopoeial revisions, and its 
pronouncements are worthy of our careful study. I have no doubt 
that they foreshadow some of the principles and standards that will 
be adopted in the revision of the U.S. P. On the other hand, one 
is impressed by the fact that the U.S. P., 8th revision, was undoubt- 
edly the model for some of the noteworthy changes in the latest 
German revision. 

The object of the present communication is to direct attention 
to the more important features of the revision as the limitation of 
our meeting necessarily precludes a detailed review of the book. 

As in the previous revisions it follows the custom of stating 
formulas, when not dosage forms, in parts by weight, even in the 
formulas for fluid extracts, and the finished products are given as 
4, 5, 9, 10, 20, 50, 100 or 500, etc., parts. The uniformity of the 
U.S. P. in this respect is lacking in the German. 

One of the noted departures in this revision is the style of giving 
formulas. The U.S. P. method of stating all the ingredients and 
quantities in the beginning of the formula and then following with 



^ Read before the New Jersey Pharmaceutical Association at Asbury 
Park, N. J., June 14, 191 1. 



ji ly ''im*^'"' } ^^/^^^ Revision German Pharmacopoeia. 327 

directions is adopted in place of the method of the previous revis- 
ions wherein each item was preceded by the amount printed in words 
and the process was elaborated throughout the formula. 

In the monographs on drugs and chemical products the style of 
treatment more closely simulates that of the U.S.F. VIII. The 
purity rubric has been adopted and is quite generally given in the 
chemical products. Here, however, one notes a lack of uniformity. 
For examples, Potassium bromide " must contain not less than 
98.7 per cent, of pure KBr " (U.S. P., 97 per cent.) and Potassium 
carbonate " in the neighborhood of 95 per cent, pure ICCO3 " 
(U.S. P., 98 per cent.), but the monographs on Potassium Iodide, 
Potassium Bicarbonate, and Potassium Nitrate, as well as those of 
other salts, lack entirely such statements of the purity requirements. 
This shows a lack of co-ordination of the work of the revision or a 
failure to adhere systematically to what appears to have been in- 
tended as one of the advanced thoughts to be adopted in the work. 

The purity rubric is extended to many of the drugs and even to 
some of the galenicals. Here the method of stating the purity 
requirement at the very beginning, preceding even the definition 
of the drug or the process of the preparation, does not appeal to 
the writer as an improvement over the U.S. P. method of including 
the alkaloidal standard as part of the definition. It strikes us as 
odd to see as the initial statement in Cantharides contains not less 
than 0.8 per cent, cantharidin," and in Cinchona " contains not less 
than 6.5 per cent, alkaloid, consisting of a mixture of quinine and 
cinchonine," or in oil of Lavender contains not less than 29.3 per 
cent. Linalylacetate," and in Extract of Hyoscyamus " contains 
0.5 per cent. Hyoscyamine " (U.S. P., 0.3 per cent, mydriatic 
alkaloids. 

In the official titles, many of the old time-honored Latinized 
vernacular names are retained and such mediaeval titles as " Borax," 
Cerussa," Lithargyrum," " Minium," still appear in this twen- 
tieth century revision. 

The German method of spelling Latinized chemical names is re- 
tained in the official titles. As examples, Baryum chloratum with 
the German synonym as Baryum chlorid, Kalium chloricum with 
Kalium chlorat as synonym and Morphinum hydrochloricum with 
morphin hydrochlorid as the German. This has always been con- 
fusing to the English-speaking nations. 

The method of classifying titles so tliat the official barks, leaves. 



328 Fifth Revision German Pharmacopoeia. { ^'"'j'f,*Jy''\fn"'°" 

flowers, roots, rhizomes, etc., appear together, is retained, and in 
each drug the title indicates the part of the plant official. A few 
changes in titles are specially noticeable. Folia Hyoscyami replaces 
Herba Hyoscyami and Rhizoma Rhei, the former Radix Rhei; 
Formaldehydum solutum is changed to F'ormaldehyd solutus, and 
Paraldehyd now appears in place of " Paraldehydnm." A note- 
worthy change in title as well as in composition is Lanolinum, which 
now becomes a mixture of wool fat 15, water 5, and liquid paraffin 
3 parts, with " water containing wool fat " as the synonym and 
the old title Adeps Lanae cum Aqua, for a mixture of wool fat 75 
and water 25, is dismissed. The Unguentum Adipis Lanse is also 
dismissed, the evident intent being that the new Lanolin shall serve 
for both of these old formulas. 

The German Pharmacopoeia recognizes the fact that the com- 
mercial chemicals sold for many purposes are legitimate subjects 
for its consideration and standardizing. We find such articles as 
crude sulphuric acid, crude copper sulphate, crude iron sulphate, 
crude potassium carbonate, and crude zinc oxide treated in suitable 
monographs. 

Nor in the consideration of vegetable drugs does the German 
Pharmacopoeia restrict its standards to the ingredients of physi- 
cians' prescriptions. It recognizes the necessity for proper definition 
for such common drugs as lavender flowers, chamomile, elder blos- 
soms, mullein, coltsfoot, walnut leaves, sage and foenugreek which, 
while only occasionally dispensed on physicians' prescriptions, are 
largely used in domestic practice and become not an inconsiderable 
portion of the dealings of the druggist. 

The International List of Atomic weights for 1910 is adopted as 
the basis for the chemical formulas, molecular weights, and the 
analytical calculations. This is the first revision of the German 
Pharmacopoeia in which chemical formulas are given. Empirical 
formulas are tabooed and throughout structural formulas are used. 
While in many places simple structural formulas, like those of the 
U.S. P. VIII, are given, in others more elaborate formulas are pre- 
sented. This is shown in the extreme in Theophyllin or Theocin 
where a modified graphic structural formula is given and a definition 
is omitted. This laxity of official definition is shown in a number 
of the monographs especially those describing organic chemicals 
and alkaloids. 

The introduction of formulas and processes for the manufacture 



ju^iyj^'im*'^™ } F^fih Revision German Pharmacopoeia. 329 

of such chemicals as the nitrate, subgallate, subnitrate and subsaUcy- 
late of bismuth, calcium phosphate, iron and quinine citrate, quinine 
tannate, etc., seems strange to us in the light of present-day experi- 
ence and economic conditions. Modern division of labor has ren- 
dered such manufacture unprofitable for the pharmacist, even if he 
should be equipped with the facilities to undertake it. 

A very commendable feature of this revision is the introductory 
chapter devoted to official methods to be followed in the making 
of such determinations, as melting point, congealing point, boiling 
point, ash, acid number, saponification value, ester value, iodine 
absorption, etc. 

Specific gravity, unless otherwise stated for special reasons, is 
taken at 15° C. compared with distilled water at 15° C. The U.S. P. 
VIII has not been followed by a single pharmacopoeia nor by the 
U. S. Government departments in the adoption of 25° C. as the 
temperature for such determinations and the writer personally 
doubts if we really assumed " an advanced " position in adopting 
25° C. or if we are now justified in retaining it alone against all 
pharmacopceial and other scientific authorities. 

Polariscope readings are by sodium light at a temperature of 
20° C. unless otherwise stated. In essential oils the figures are 
for reading with 100 mm. tube. 

Microscopic measurements are stated in microns the 11 being 
equal to i/iooo mm. 

The degree of fineness of drugs is indicated by a scale of num- 
bers varying from No. i to No. 6, No. i being coarsely comminuted 
drugs passing through a sieve whose meshes are 4 mm. apart, and 
No. 6 being finely pulverized drugs passing through a sieve whose 
meshes are about 0.15 mm. apart. 

For counting drops the normal drop counter of the Brussels Con- 
ference is adopted, and the method of stating doses is retained as 
in the previous revision, namely, the largest single dose and the 
largest daily dose. 

Possibly the greatest advance is shown in the monographs treat- 
ing of the organic drugs. Here we note first the innovation of giv- 
ing the botanical authorities for the plant names, and these are quite 
generally the more recently accepted authorities. Secondly, and 
most praiseworthy, is the microscopic descriptions so' generally in- 
cluded. These evidence the great advances made in the science of 
pharmacognosy since the last revision. Another commendable feat- 



330 Fifth Revision German Pharmacopoeia. [^'''\)yS^\^\"'^' 

ure is the statement of ash content quite generally given. The 
method of stating the amount of alcohol soluble content in sucn 
drugs as asafetida and benzoin is to be commended as clear and 
worthy of copying in the U.S. P. Our Pharmacopoeia directs that 
benzoin be " almost wholly soluble in 5 parts of warm alcohol." 
The German Pharmacopoeia that on thorough extraction with boil- 
ing alcohol the residue on drying must not exceed 5 per cent, of the 
benzoin." 

The Ph. Gr. rec^uires for asafetida that " on thoroughly ex- 
tracting with boiling alcohol, and drying the residue at 100° C. it 
shonld not exceed 50 per cent, of the amount taken. The ash is 
limited to " not over 15 per cent.," the U.S. P. states " not less than 
50 per cent, should dissolve in alcohol," and the ash limit is not more 
than 10 per cent. 

Assay processes are greatly extended and improved and new 
ones are added for a great many articles not heretofore assayed. 
As examples of the extent to which assaying has been extended may 
be mentioned mustard paper and pomegranate bark. The selection 
of the articles assayed, however, is not readily understood. As, for 
example, assays are given for oils of cinnamon, lavender, santal and 
mustard, the latter being the synthetic oil, yet no assays are given 
for oils of anise, lemon, peppermint or rosemary ec[ually important 
and assayable. In the alkaloidal assays where the alkaloid is esti- 
mated by titration iodeosin is the indicator commonly directed. 
Where assay processes are not available, not infrequently identifi- 
cation tests are given. As example, Borntrager's reaction for 
oxymethylanthroquinones is given as a characteristic test for the 
fluid extracts of frangula and cascara sagrada. 

The attempt to follow the protocol of the Brussels International 
Conference is evidenced not only in the adoption of the Normal 
Drop Counter recommended but also in the adoption of many of 
the formulas and standards for potent drugs. Such adoption is indi- 
cated by a subtitle in Latin with P. I. appended. However, there 
are a number of instances where deviation in menstruum from the 
international 70 per cent, alcohol is made, yet the P. I. is ap- 
pended. Example, Tinctura Cantharidis and Tinctura lodi in which 
alcohol is directed. In a number of other cases where some devia- 
tion has been allowed the P. I. is not appended as, for example, 
Tincture of Aconite, although 10 per cent, drug is not indicated as 
international probably because no assay is given. Nux Vomica and 



^"^ju^^'iSi*'^'" } ^' '^f^^^ Revision German Pharmacopoeia. 331 

Strophanthiis are not marked P. 1. yet the tinctures made therefrom 
are both marked P. I. 

To Tincture of Colchicum is appended the instruction that when 
Vinum Colchici is directed the tincture is to be given therefor and 
to Tincture of Ipecac is a similar instruction given that when Vinum 
Ipecacuanhse is ordered the tincture is to be dispensed. The wis- 
dom of such modification of physicians' orders is not above ques- 
tion and also the consistency of an agreement that " a potent medica- 
ment should not be prepared in the form of a medicinal wine " 
and then the same convention immediately proceeded to adopt an 
international standard for wine of antimony. Is there any reason 
why Vinum Ipecacuanhse should be eliminated from medical prac- 
tice and ''Vinum Stibiatum " retained? 

The admissions to the official list are interesting and wmle 
some are but little known or used in the United States others are 
extensively used. In the selection of pharmacopoeial titles the Ger- 
mans are not handicapped by product patents and trade-mark laws, 
and if the chemical name is too lengthy or not suitable for an 
official title they simply take the common or trade name, even if 
considered proprietary, and adopt it as the official title. This is 
shown in the present revision by the adoption of such titles as 
Stovaine and of Ansesthesin for para-amino-benzoic-ethylester. 
Even when the chemical name is Latinized as the official title the 
common or trade-mark name is given as an official synonym. Thus 
under Acidum Acetyl-salicylicum, Aspirin is so given and imder 
Acidum diacetylbarbituricum, veronal is stated as the synonym. 
Among the other more important admissions we note dionin, heroin, 
colloidal silver, silver proteinate, beta eucaine, lactophenin, arsa- 
cetin, atoxyl, novacaine, phenolphthalein, tropacocaine hydrochlo- 
ride, theocin synthetic and. suprarenin hydrochloride which latter 
may be either the natural from the gland or the synthetic which is of 
doubtful value. Some of the additions such as gallic acid, guaiacol 
carbonate, hexamethylene tetramine, solution of hydrog'en peroxide 
and cascara sagrada are so well established in American practice that 
we think our German friends at least a decade slow in their adop- 
tion. Concerning cascara an inconsistency in the title is shown ; 
the drug is recognized as " Cortex Rhamni Purshian?e," yet the 
fluid extract is entitled " Extractum Cascanx Sagrad?e fluidum." 

Collemplastrum is a new title for the rubber adhesive plasters 
and two formulas are given collemplastrum adh^esivum and col- 



332 Fifth Revision German Pharmacopana. { "^"jf,?" '■'ign*'""' 

lemplastrum zinci, for the two popular plasters, surgeons adhesive 
plain and with zinc oxide. Their formulas contain caoutchouc, wool 
fat and copaiba balsam, with powdered orris root as a filler, and are 
well worth experimenting with as a substitute for our official 
adhesive plaster that is never made. 

Peanut oil is introduced and is directed as an ingredient in some 
of the plasters, ointments and liniments, but it is to be noted that 
for camphorated oil the German Pharmacopoeia still adheres to olive 
oil 

Among the articles dismissed we note hydrobromic acid, dried 
egg albumin, tar water, ferric chloride, jaborandi, poppy capsules, 
vanilla, solution ammonium acetate, syrup of poppy, wines of col- 
chicum and ipecac. 

The galenical preparations are classified into numerous distinctive 
classes and each class is headed by a short descriptive paragraph or 
chapter setting forth its definition and such general instructions as 
are appropriate. 

The German still lovingly adheres to his idol, maceration, and 
percolation, as yet, receives but scant consideration in his pharmaco- 
poeia. While percolation is directed in a few formulas such as the 
fluid extracts, where the rate of flow is fixed at 30 drops per minute, 
yet in other important extractions such, as for example. Extract of 
Nux Vomica, maceration and expression is directed. 

The requirements or some of the important articles are briefly 
given so as to be compared with those official in the U.S. P. 

Alcohol is 91.29 tO' 90.09 per cent, by volume. 

Diluted Alcohol is 69-68 per cent, by volume, thus corresponding 
closely with the 70 per cent, alcohol recommended by the Brussels 
Conference as a universal menstruum for tinctures of potent 
remedies. 

Acid Benzoic is the sublimed and from Siam Benzoin, and tests 
are given to detect the synthetic. The U.S. P. recognizes both with 
preference for the synthetic. 

Acidum Carbolicum is still retained as the title for " Phenol." 

Hydrochloric Acid remains " about 25 per cent. HCl " and the 
diluted 12.5 per cent. 

Phosphoric Acid remains 25 per cent. HgPo^ ; the U.S. P. is 85 
per cent. 

Aloe is restricted tO' the inspissated juice of the leaves of " Afri- 
can species of Aloe " with omission of the exact botanical source. 



^"juiy^'im*'^'"'} ^^/^^^ Revision German Pharmacopoeia. 333 

Ammonium Carbonate like the U.S. P. is the academic statement 
rarely if ever found in commerce. 

Cantharides is required to contain 0.8 per cent, of Cantharidin. 
The assay process has been improved by recrystallizing the product 
from Acetone, but it still does not yield a colorless and pure product. 

Sulphuric Acid is 94 to 98 per cent. H2SO4, the crude 91 per 
cent, and the diluted 15.6 to 16.3 per cent. 

Capsules are described as of two forms, the platter or cup-shaped 
made of wheat flour or wheat starch, and the hollow gelatin capsule. 

Catechu is retained ; no Gambir for the Germans. 

Cinchona is restricted to the Bark of Cinchona Suiccirubra 
Pavon. 

Quinine Sulphate : The chemical formula is given as containing 
8 molecules of water. The U.S. P., while giving the formula as 
7H2O, in the text allows a loss in drying, " indicating not more than 
8 molecules of water." 

Cinnamon : The Ceylon bark replaces the Chinese and the oil ol 
Ceylon Cinnamon is now the German ofiicial oil of cinnamon. 

Fluidextracts : But four new ones have been added, namely, 
cascara, cinchona, granatum and simaruba. The Cinchona contains 
17 parts of Diluted Hydrochloric Acid in 100 and is essentially the 
formula of the British Pharmacopoeia. 

Sassafras is the wood of the root. 

Solution of Iron Albuminate : Fresh hen's egg albumin replaces 
the dried of the previous edition. The variability of the commer- 
cial dried albumin and disagreeable odor possessed by many sam- 
ples necessitated this change. 

Liquor potassii hydroxidi and Liquor sodii hydroxydi are both 
" about 15 per cent." while the U.S. P. are only about 5 per cent. 

Magnesium Carbonate : Two chemical formulas are given show- 
ing varying mixtures of magnesium carbonate and hydroxide, the 
one with 3 molecules of HoO and the other with 4. The U.S. P. 
gives the latter formula but with 5 molecules of water. Probably 
both authorities give academic formulas that do not describe the 
trade article. 

Opium is required to contain " not less than T2 per cent, of 
morphine after drying at 60° C." It would be rather difficult to dry 
a substance like opium uniformly at that temperature. 

Powdered Opium is required to contain 10 per cent, of anhydrous 
morphine. The U.S. P. standard 12 to 12.5 of crystallized morphine 
varies but slightly from the international agreement. 



334 I'ifi^i Revision Gcriiiaii riianiiacopaicL {'^■'^,•^^y,^.Ju*'''"■ 

Pill of Aloes and Iron^ very similar to the U.S. P. formula, is 
retained, 

Sarsaparilla is continued as the Honduras " variety. 
Taraxacum is the " root with herb " collected in the spring- before 
flowering. 

Artificial Carlsbad Salt remains in the German Pharmacopceia. 
This is an N.F. preparation that has been severely criticized because 
a factitious product. 

Sapo Kalinus remains quite properly a linseed oil soft soap. 

Scopolamine hydrobromide is the Isevarotory " hyoscine," and the 
latter title is not given. 

Ergot is directed to be kept for not more than one year, and 
not kept in the powder form, but powdered as needed. 

Strophanthus : Seed of S. kombe Oliver only, but in the tincture 
the protocol is blindly followed despite its error, and a lo per cent, 
drug tincture is made with 68 per cent, alcohol and the seed not 
previously defatted. 

Nux Vomica : The standard is 2.5 per cent, mixed alkaloids 
strychnine and brucine, of which it is assumed that a little more 
than half is strychnine. 

Serum Antidiphthericum : Here the serum antitoxin and the 
dried antitoxin are recognized but the concentrated globulin form 
which is so extensively used in the U. S. is not mentioned. 

Physiological Salt Solution is given as Sodium Chloride 8. 
Sodium Carbonate 0.15, water 991.85 parts, filtered and sterilized. 

Spirit of Lavender is directed to be made by macerating for 24 
hours I part lavender flowers and alcohol 3 and then distil ofif by 
the water bath 4 parts. This is an impossible formula and evidently 
there has been an omission of the 3 parts water directed to be added 
in the 4th Revision. 

Tincture of Ipecac : A new introduction to meet the theoretical 
user of the P. I. 

Each formula is accompanied by a description of the product 
and not infrequently this gives in addition to the color, consistence, 
taste, etc., also the specific gravity and the percentage of extractive 
and ash, and any distinctive characteristic reaction or test. 

Several of the important features of this revision are contained 
in the chapters of the appendix. The first being the list of elements 
and atomic weights. The second is the chapter on reagents and 
volumetric solutions. The third chapter is a list of reagents and 



^""'ji^yfian*™'} Lactic Acid Ester of Santalol, etc. 



335 



volumetric solutions for medico-chemical examinations. This is one 
of the most commendable features of this revision and places in a 
compact schedule these reagents and tests and should prove a valua- 
ble aid to the busy practitioner or pharmacist. The classification here 
is according to the subjects of investigation, the first sub-heading 
being the reagents for urine analysis, and this is sub-divided under 
paragraph headings directions for albumin, for sugar, for pentoses, 
for acetone, for acetic acid, for urobilin, for urobilinogen, for gall 
coloring matters, for indican, for carrying out the diazo reaction, for 
iodine, for salicylic acid and for blood. The second classification 
is for the investigation of stomach contents. The third for the 
examination of blood. The fourth is for the examination for bac- 
teria and protozoa, and here formulas are given for the necessary 
stains and reagents and the standards are here given for the cedar 
oil, Canada balsam and xylol suitable for microscopic investigations. 

Another chapter of the appendix is a table of specific gravities 
of the official liquids at temperatures from 12° to 25°. Although 
doses are given with each monograph or formula in the body of the 
book, a table of maximum doses for adults is given in the appendix. 
Another table is devoted to a list of the deadly poisons that must 
be kept under lock and dispensed with great caution. Still another 
table is devoted to other less poisonous or dangerous medicaments 
that one should beware of. An extensive list of synonyms and 
less used names is one of the important tables included in the 
appendix. 



THE LACTIC ACID ESTER OF SANTALOL AND OTHER 
SANTALOL COMPOUNDS.^ 

By Frederic S. Mason, B.Sc, Ph.G., M.D., New York. 

I should have liked to have introduced the subject of my paper 
by a short review of the history of sandalwood and its oil, for 
with ambergris and musk, sandalwood is one of those natural 
products used from very remote ages in perfumery and medicine. 
I have been interested in sandalwood for over twenty-five years, 
having been one of the first to make an investigation of the sources 
of supply in India, Malaysia, Timor and Western Australia, which 
countries I visited on two occasions for the specific purpose of 
determining the cause of the variations observed in the laboratory, 

^ Read before the New York section of Am. Chemical Society, 5th May, 191 1. 



336 Lactic Acid Ester of Santalol, etc. J ^'"•jfr'ioiu''"' 

when examining the oils obtained from wood bought on the London 
market. In recent years, a pecuhar malady called in Mysore spike 
disease " attacked the sandalwood ; parasitic roots of other trees 
attaching themselves underground to the sandalwood roots even at 
from one to one hundred feet distance. This disease at one time 
bid fair to exterminate these valuable trees, but the Mysore govern- 
ment, which derives an important revenue from this source, is now 
engaged in heroic efforts to save them. 

My time, however, being limited to twenty minutes, I refrain 
from enlarging on this subject and must refer those who are inter- 
ested to the contributions to materia medica which I have published 
from time to time in the Pharmaceutical Journal of Great Britain, 
and more recently in the American edition of the Tribune Medicale 
of November, 1909. 

It is now recognized that the most valuable oil is obtained from 
the heart wood of the true Santalnni album growing on the higii- 
lands of Mysore in Southern India, and it is with this product that 
I am dealing in the present paper. 

In confirmation of what I have already published on sandalwood 
oil distilled in India, I will quote from Schimmel's Semi-annual 
Report of October, 1910, since it confirms much that I have already 
written on the Sandalwood of Mysore, although reference is here 
made to an outlying territory : The distillation of sandalwood oil 
appears to be an ancient industry in Southern Kanara, especially in 
the district of Udipi, but it is steadily declining. Natives from 
Udipi attend the auctions in Mysore and Coorg every year, and 
attract attention by their bids, which are often extravagantly high, 
especially for Coorg wood. But not all the wood bought by these 
dealers is distilled by them: a portion of it they resell to Bombay. 
It is said that the distillers also use smuggled wood (sandalwood 
being a monopoly of the State of Mysore), besides which sandal- 
wood trees may occur here and there in the district of Kanara. 

" The oil industry is centred principally in the district northeast 
of Karkul up to the foot of the Ghats. 

" For distilling purposes, the wood is cut into chips and placed in 
the still. Water is then added and the distillation of the same 
charge is continued uninterruptedly day and night for a whole 
month. Fresh supplies of water, consisting of the luke-warm water 
taken from the cooling vessel, are poured into the still about 15 
times every 24 hours. The oil-yield is said to be as follows : 



Am. Jour. Pharm. 



j Lactic Acid Ester of Santalol, etc. 



337 



July, 1911. 



Roots 

Jugpokals . 
Ain Chiltas 



about 4.34% 
, " 2.60% 



" The oil is partly brought to market at Udipi and partly at 
Mangalore. Almost all the oil is shipped by steamer to Bombay, 
whence it is exported to the Persian Gulf and to China. 

" It hardly needs to be pointed out that under the primitive 
conditions of distillation wliich have been described, it is impossible 
to obtain any really good sandalwood oil. Owing to the prolonged 
duration of the distilling process, decomposition-products must 
necessarily be formed, which must injuriously affect the quality of 
the oil and be equally unfavorable to its color and odor." 

Santalol, in two isomeric forms, occurs as the alcohol of the 
East India sandalwood oil, and is recognized by all therapeutists as 
the chief active component of this oil. The older pharmacopoeias 
have been content to establish a standard based on the specific 
gravity and its solubility in alcohol, but the present U.S. P. requires 
90% of santalol and states that the oil is laevogyrate — its angle of 
rotation should not be less than — 16° nor more than — 20° in 
100 Mm. tube, at a temperature of 25° C. This differentiates the true 
oil of the Santaluin album (N.O. Santalaceae) from those derived 
from species of sandalwood or adulterated with cedar and other 
spurious oils. 

Chapoteaut, in 1879, read a paper before the Paris Societe de 
Chimie, and was the first to call attention to the fact that sandal- 
wood oil was composed chiefly of alcohols, from which he was able 
to make a series of esters with appropriate acid anhydrides. The 
empirical formula of the santalol he then referred to, he determined 
to be Ci.r.HooO. He also isolated another body, to which he ascribed 
the formula C^-li^^^y ^^^^ these findings were verified by Chapman 
& Burgess (Proceedings of the Chemical Society, London). Parry 
followed up Chapoteaut's work some years later, and Continental 
chemists have since shown that the pure oil is chiefly composed of 
a mixture of tlie santalols together with two isomeric sescjuiterpene 
alcohols. Guerbet speaks of an alpha- and beta-santalene, which 
both combine slowly with glacial acetic acid when heated in sealed 
tubes. The hydrochlorides of santalol Cir,H242 HCL, have an optical 
rotation in an opposite direction to the original sesquiterpenes, that 
of the alpha-santalcnc hydrochloride being 6° i/, and that of beta- 
santalene hydrochloride 8°. Alpha-santalcne gives only one crystal- 



338 Lactic Acid Ester of Santalol, etc. { ^"\,;u";\9u*'''" 

line nitrosochloride at 122° C, and is insoluble in alcohol. Beta- 
santalene gives two isomeric nitrosochlorides, both of which are 
soluble in alcohol. The two santalols, isolated together from other 
constituents of the oil as phthalic esters, can only be separated from 
each other after saponification by fractional distillation under 
reduced pressure. Thus obtained, the alpha-santalol boils at 300°- 
301° C. (as pointed out by Chapoteaut in his first paper of this 
subject), has a density of 0.9854 at zero centigrade and a rotation 
of — 1° 20'. Beta-santalol boils at 309°-3io° C, and has a density 
of 0.9868 at 0° C. and the rotation is — 56°. Dehydrating agents, 
such as acid potassium sulphate or phosphoric anhydride, remove a 
molecule of water, converting them into their respective isosantalenes 
C^^Ho^. Alpha-isosantalene boils at 259°-26o° C, so that the alpha 
and beta compounds approach very nearly to the essences of copaiba 
and cedar. Hugo and Soden have also given considerable time to 
the examination of sandalwood oil. F. Muller claims to have 
isolated a new terpene C,H]4, which lie calls santene. This has a 
Sp. gr. of 0.871, and boils between ]39°-i4o°. It forms two 
polymeric crystalline nitrosochlorides, one blue and the other color- 
less. It also gives a solid hydrochloride melting at 80° C, thus 
conforming with the reactions of other terpenes. This terpene is 
probably derived during distillation from teresantalic acid, since 
when that acid is heated under a reflux condenser, COo is found to 
be given off and on distilling, santene is obtained. Muller also found 
a ketone, santalone Ci^H^f-O, boiling at 214° -21^° C, isomeric 



with jasmone. 

To summarize, the following definite compounds have been 
isolated from sandalwood oil: (per kilogr.) 

Santalenes " a " and " I3 " 60 

Santalols " a " and " b " 800 

Santalal 30 

Acids in the state of esters (formic, acetic, san- 

talic, teresantalic) 30 

Undetermined strongly odorous bodies boiling 

at i30°-220° C 3 

Undetermined products boiling about 320° C. 

(hydro-carbons, alcohols, ethers, resinous 

products) 77 



1000 



^'"'ji^rian*'"""'} ^^^^^^^ ^^^'^ S^^^^^o^' 339 

From a series of examinations made by Sodan and Muller, these 
authorities suggest the following constants for sandalwood oil : 

Specific gravity 0-975 to 0.982 

Optical rotation 16° to 20° 

Refraction index Not below 1.5030 

Santalol (total) At least 90 per cent. 

Esters as santalyl acetate 4 to 6.5 per cent. 

Rotation of first and second fractions of 10 per 

cent Not below 16° 

Sandalwood oils found on the drug markets of London and the 
Continent are now sold with a guarantee of 94 per cent, of santalol,. 
but this guarantee should not be taken too seriously, since repeated 
examinations of various brands show that they vary between 90.9 
and 93.6 per cent, of santalol with from 1.5 to 6 per cent, of the 
esters of santalol. Occasionally an oil is found which gives as high 
as 98% of santalol. These variations explain the variable specific 
gravity of the oils found in commerce. The U.S. Pharmacopoeia 
gives the specific gravity as .965 to .980 at 25° C. We see, there- 
fore, that the requirements of the U.S. P. are moderate and allow 
for variation in the percentage yield of santalol. 

Since the santalols are responsible for the medicinal efi^ects of 
sandalwood oil, it is with these definite products that we have chiefly 
to deal. Sandalwood oil and santalol, however, are not well toler- 
ated by most patients, and chemists have, in recent years, attempted 
to form compounds with these alcohols in order to obtain less irri- 
tating esters, while retaining their beneficial medicinal effects. Many 
processes have been patented, the patentees claiming that santalol 
esters are better tolerated and less objectionable in taste, while their 
therapeutic activities are retained. The general principle for the 
production of these esters is to act on the santalol with an anhydride 
or by obtaining compound esters by action between a santalol halogen 
and an alkaline ethylate, phenylate, etc. Solid esters in fine white 
crystalline needles, such as the santalol ester of allophanic acid, 
containing 72 per cent, of santalol, have been obtained. The neutral 
esters of the aromatic acids, however, are the best known, and 
amongst the rather long list, the following have had a passing 
notice and are used to some extent : Santalol benzoate, salicylate, 
cinnamate, succinate. A ])hosphate has also been obtained. 

As these santalol compounds are incompatible with alkalies, the 



340 Lactic Acid Ester of Santalol, etc. { '^"'•.,f,?v%9u*"°' 

theory of their activity is based on the supposition that the alkalinity 
of the duodenum breaks them up, liberating nascent santalol. The 
therapeutic dose, however, has to be somewhat increased according 
to the molecular weight of the ester. These compounds of santalol 
are known under various trade names and need not enter into 
discussion here. 

In considering a compound of santalol for medicinal use, wc 
should look for one which will not interfere with the gastrointestinal 
digestive processes and which will be finally eliminated during 
metabolic changes, as santalol, Coo and HoO. This I think is best 
realized in the lactic acid ester of santalol (CH3CHOHCOO, 
C15H05), which represents 69.74 per cent, of pure santalol. It has 
the advantage of being more agreeable to the taste than sandalwood 
oil or santalol, it is well tolerated and can be administered in the 
form of capsules. Like other lactates, the lactic radical is com- 
pletely consumed in the economy. It renders the urine somewhat 
alkaline, diminishes the overstimulation of the renal parenchyma 
and does not occasion the pain in the back so often complained of 
by patients to whom sandalwood oil is administered. 

While lactic acid does not react directly with santalol, its primary 
and secondary anhydrides, the so-called lactid, do so under certain 
conditions, and a patent has been granted for the process of manu- 
facture of the santalol lactate in the United States and England and 
is pending in Germany and France. In practice, this is obtained by 
driving ofif from syrupy lactic acid 25 per cent, of the compound 
with water, leaving the primary and secondary anhydrides, the 
dilactic anhydride of Pelouse, or lactid, which is solid to 25° C. 

It is an advantage to use a slight excess of the lactid over and 
above the theoretical combining molecular weights and this leads to 
som.e difficulty in the purification of the final product, which is one 
of the essential points of the patent, for it is exceedingly bitter and 
disagreeable to the taste and can only be removed from the santalol 
lactate with difficulty. Primary and secondary lactic anhydrides, 
therefore, are placed in contact with the santalol, in the molecular 
proportions necessary for chemical combination and heated in a 
partial vacuum to a temperature not exceeding 130° C. 

For therapeutic use, and for reasons of economy, it is considered 
unnecessary to obtain an absolutely pure santalol lactate, and in its 
manufacture, U.S. P. sandalwood oil containing at least 90% santalol 
was used, rather than pure santalol. 



'^"jfurim*''"*} -^^^^ ^-^^^^ of Santalol etc. 341 

As the result of a number of experiments, the following was found 
to yield a santalol lactate of from 92 to 95% purity (according to 
the percentage of santalol in the sandalwood oil used) and was 
finally adopted : 

Sandalwood oil in the following proportions (weight) iio grams 
(equivalent to 100 grams santalol in the sample) and 120 grams of 
solid anhydrides (lactid) of lactic acid, were placed in a flask attached 
to a Liebig condenser. Heated in a partial vacuum to 108-110° C, 
a primary reaction occurs with ebullition. The temperature was then 
gradually raised to 125-130° Cent., when a more violent secondary 
reaction took place. The temperature was maintained at 130-135° C. 
for twelve hours. There was no distillate at this temperature. The 
contents of the flask were then boiled repeatedly with distilled water 
for several hours to remove the bitter taste of the excess of lactic 
anhydride present. 

The product was washed with a 1% solution of NaHCOg, then 
with 1% HQ; washed again with distilled water until it gives no 
opalescence with AgNOg, filtered and estimated for the proportion 
of combined santalol and lactic acid. 

THE THEORETICAL PERCENTAGE COMPOSITION OF SANTALOL LACTATE. 

Santalol A " and B " C^Ji^fiU (molecular weight 220.53), 
combines with lactic acid CH3CHO HCOOH (molecular weight 
89.37) or as lactid C3H4O2 (molecular weight taken as 72), to form 
a monobasic compound of santalol lactate C3H5O3, C15H25 (molec- 
ular weight 291.90). 

The theoretical percentage of the lactic radical in santalol lactate 
therefore is 30.28. 

The theoretical percentage of santalol in santalol lactate therefore 
is 69.74. 

The findings of a series of 14 analyses show that the product 
made by my process closely approximates these figures. 

The lactic acid ester of santalol has the following characteristics : 
It is reddish brown in color, possesses a sp. gr. of from 1.050 to 
1.065, is neutral in reaction, but with a slightly bitter and acidulous 
taste (possibly due to slight impurity). It is soluble in alcohol, 
ether, chloroform, acetone, carbon bisulphide, and carbon tetra- 
chloride, but' insoluble in water. It has a pleasing but peculiar odor, 
dififering entirely from either of its constituents and slightly recalling 
that of the terpenes distilled from the Apimn petroselnium or com- 



342 



Rapid Deterniination of Sulphuric Acid. \ 




mon parsley. On heating with alcoholic solutions of KOH or NaOH, 
it is saponified with liberation of santalol, but is not affected by weak 
mineral or organic acids. Its boiling point is between 250° and 260° 
C. at 60 M.M. 

I do not pretend to have obtained an absolutely pure santalol 
lactate, but the commercial process described is practical and the 
product all that is required for medicinal use in place of sandal- 
wood oil. 

Hotel Brevoort, May 5, 191 1. 



RAPID DETERMINATION OF SULPHURIC ACID WITH 



Every chemist in general will agree that up to the present our 
methods of gravimetric, and volumetric analysis are apt to have 
some phase where the accuracy is in doubt, where the reaction is not 
fully, or in some cases purely hypothetical, and therefore not abso- 



lutely correct ; we therefore go through journals and chemical 
literature to find our way out of a labyrinth of reactions which take 
place by a simple precipitation of two bodies chemically acted upon 
according to the laws which govern these reactions, visible and ob- 



THE POROUS CLAY CRUCIBLE. 



By Frederick Klein, Ph.D. 




, POROUS 
h-CLAY CRUCIBLE 
p-THE PRECIPITATE 
I^LASS BELL JAR SO 
CALLED CARBON FILTER 



m 

FIG I 



SUCTION PIPE 
POR PUMP WITH 
HEAVY TUBING 



Rapid Determination of Sulphuric Acid. 343 

scure, to all our scientific endeavors, methods, instruments, abil- 
ity and chemically reasoning. 

One of the methods which is of the greatest importance and in 
practical use all over the chemical world is the sulphur determination 
by barium salts, the considerable time and ability spent to perfect 
this one method alone would fully prove the correctness of the 
statement above. In one of the latest Chemical News, the prime 
and most distinguished German chemical paper Che in. Ztg., No. 135, 




FIGI SHOWS 



of November 12, on page 1201, we read an article: again stating 
that the problem of the absolute precipitation of the sulphuric acid 
with barium salts is still problematic and requires considerable skill 
and comparatively an absurd length of time to obtain concordant and 
satisfactory results. 

I therefore with pleasure can state, that through the aid of techni- 
cal progress we have succeeded and obtained a most charming chemi- 
cal device in the form of a porous clay crucible manufactured by a 
firm in one of the New England States, and therefore an American 
production of the highest esteem, and importance to the chemist. 



344 



Rapid Determination of Sulphuric Acid.^ 



Am. Jour. Pharlu. 
.Iiilv, 1911. 



because it fully eliminates the filter paper process, which is one of 
the most objectionable features in most of the chemical procedures 
and analytical work of all kind, every chemist will welcome this por- 
ous crucible because we all know the difficulty in burning filters, in re- 
gard to the ashes and at last, but not least, the reducing action of 
the carbon of the filter which is highly objectionable, especially in 
the sulphur determination. These and many other objections which 
are daily observed in regard to these methods have led me to devise 



a new porous crucible which enables the chemist to make a dozen or 
even more sulphur determinations in comparatively the same length 
of time spent to make a single filter determination considering all 
points of importance in regard to boiling and addition of barium 
salts, etc. 

Taking the advice of " Hintz " and Weber " in their extensive 
study of this especial method, if we operate under the same 
caution and condition, there arises one and the same inaccuracy 
which can be tolerated in this method and by the other methods 
and greatly increase the accuracy after all. 





t 

HEAVY RUBBER 
TUBING 



HEAVY 
^RUBBER 
TUBING 



FIG 3 



^'"*ju'iy%9n'''"™'} ^^/'^^ Determination of Sulphuric Acid. 345 

I therefore describe this most simple and rapid determination 
of sulphuric acid, taking normal sulphuric acid as a standard with 
49.05 Gm. of H0SO4 to the litre : 10 ex. of n/^ — H2SO4 are trans- 
formed from a burette or pipette to a beaker of 300 or 400 ex., the 
acid is then diluted with three or four times or more by volume of 
distilled water and boiled for a few minutes ; to this solution is 
added a few c.c. of cone. HQ or HNO3, stirred, and while boiling 
add the boiling or hot solution of barium chloride or nitrate 10 or 
15 c.c. (10 per cent, solution) ; stir and mix, and keep mixed solu- 
tion boiling for a further few minutes ; then transfer to a warm 
place or water bath if convenient to have for settling of the macro- 
crystalline ppt. While the ppt. settles in water bath the porous 
crucible is heated and weighed which can be done very easily. I 
generally weigh the crucible under the same condition without the 
use of an exsiccator and was able to obtain very satisfactory results. 

The weighed crucible is then attached to a water pump of any 
kind with the so-called carbon filter with rubber stopper, and a mod- 
erate stream of water will filter the hot barium sulphate ppt. abso- 
lutely clear through the porous clay crucible, leaving ppt. nearly 
white, and after washing with hot water, or better, slightly acidu- 
lated water to free the ppt. from barium chloride or nitrate which 
can be tested for such with silver nitrate or diphenylamin solution, 
in the filtrate. The porous crucible with ppt. is then carefully heated 
with a Bunsen burner and after moisture has been driven off the 
crucible can then be strongly heated and weighed to constancy. 

I have worked out a table based on the principle of normal 
sulphuric acid 49.05 Gm. of H^SO^ to 1000 c.c. Aq. Dest. figuring 
the acid from barium sulphate from 9 c.c. tO' 11 c.c. This will 
enable the chemist to know exactly the strength of acid to dilute 
or to make stronger if necessary. Ten c.c.^ which averages to about 
0.4905 Gm. H0SO4, is about or approximately the sufficient amount 
of any sulphate to be analyzed, with exception of sulphate ores to 
more conveniency in some cases to i Gm. and more. 

This table can also be used for any sulphur analysis considering 
that the BaS04 as noted in the table corresponds to the product 
analyzed. 

The crucible as such can be used for the analysis of different col- 
loidal and semicolloidal ppts. with the same accuracy and less time. I 
have tried the crucible for different analyses and found it to be 
satisfactory. 



34^ Rapid Determination of Sulphuric Acid, ^^""-/^"f^^^^""^- 

NORMAL SULPHURIC ACID. 

Factor 0.137 = for sulphur. 
Interpolation table between 9 c.c. and 11 c.c. 





BaSOi= 233. 5 




H2SO4 =49.05 


= 98.1 


cbcm of n/iH2S04 contains 


cbcm of n/iH2S04 contains 


2 

H2SO4 in 1000 c.c. 


9.0 


C.C. 1.05075 BaSOi 


9.0 c 


\c.o.44i45 H.SO4 


44.1450 


9.1 


" 1.062425 " 


9.1 


" 0.446355 


44-6355 


9.2 


" 1.07410 " 


9.2 


' 0.451260 


45.1260 


9-3 


" 1.085775 


9-3 


" 0.456165 


45-6165 


9.4 


" 1-09745 


9.4 


" 0.461070 


46.1070 


9.5 


1.109125 


9-5 


" 0.465975 


46.5975 


9.6 


" 1. 12080 " 


9.6 


' 0.47088 " 


47.0880 


97 


" 1-132475 


9-7 


" 0.475785 


47-5785 


9.8 


" I-14415 


9.8 


" 0.480690 4 " 


48.0690 


9.9 


" 1-155825 


9.9 


" 0.485595 


48-5595 


lO.O 


" 1. 16749 


lO.O 


' 0.49050 


49.0500 


lO.I 


" 1-179175 


10. 1 


' 0.495405 


49-5405 


10.2 


1. 19085 


10.2 


" 0.50031 


50.0310 


10.3 


" 1.2025 " 


10.3 


' 0.505215 


50.5215 


10.4 


" 1. 2142 " 


10.4 


" 0.51012 


5 LOT 20 


10.5 


" 1.22587 


10.5 


' 0.515025 


51-5025 


10.6 


" 1-23755 


10.6 ' 


' 0.519930 


51-9930 


10.7 


1.24922 


10.7 


" 0.524835 


52.4835 


10.8 


" 1.26090 


10.8 


" 0.529740 


52.9740 


10.9 


" 1.272S7 


10.9 


' 0.534645 


534645 


I I.O 


" 1.28428 


1 1.0 


' 0.539550 


53 -95 50 



BaS04 X 0.137 = Sulphur. 

BaSOi X 0.34286 = Factor = Sulphur trioxide. 
BaSO* X 0.420 = Factor = Sulphuric Acid. 

To multiply factor with Barium Sulphate gives either S, SO3 or H2SO4. 
The following is an addition to the interpolation table : 



I. 


2. 


3- 


4- 


9.0 to 9.1 


9.9 to lO.O 


lO.O to lO.I 


lo.i to 10.2 


0.051917 


LI 56992 


1. 1 68667 


1. 180342 


0.053084 


Li58i^9 


1. 169834 


1. 181 5092 


0.054251 


LI 59326 


I.I7IOOI 


I 182676 


0.055418 


1.169493 


LI72I68 


L 183843 


0.056585 


1.161660 


I-I73335 


I.1850IO 


0.057752 


LI 62827 


I- 1 7450 


L186177 


0.058919 


1. 1 63994 


LI 75669 


1. 1 87344 


0.060086 


I.165161 


LI 76836 


I.1885II 


0.061253 


1. 1 66328 


1. 1 78003 


LI 89678 


0.06242 


1. 167495 


I.I7917 


1. 1 90845 


Example : 


it has been found 


upon using 10 c.c. 


of H.SO^ that 



I -1 73335 BaSOj^^ by weight, was obtained. Upon consulting table 3 
this denotes that the solution of H^SO^ is 5/100 or 0.05 in 10 c.c. too 
strong. 



^"•ju^irim*"""} ^^^^ Adrenalin Patents Valid. 347 



THE ADRENALIN PATENTS VALID. 

THE UNITED STATES CIRCUIT COURT SO DECIDES. 

When the physiological and therapeutic value of the suprarenal 
gland had become fully established, several prominent chemists, 
believing its valuable properties to be due to an active principle, 
studied strenuously to isolate it. Two at least came very near 
success. It remained for Dr. Jokichi Takamine,. however, to achieve 
the sought-for result, and he secured basic patents covering the 
substance, its salts and solutions, simultaneously publishing his 
methods. Other investigators afterward claimed to have isolated 
the active principle, and there appeared on the market, in addition to 
Adrenalin, similar preparations under other names. 

It became a much-mooted question whether Dr. Takamine was 
entitled to priority, and whether the patents were valid. Parke, 
Davis & Co. purchased the Doctor's rights in consideration of a 
royalty, under agreement that payment of the royalty should cease 
if the patents were invalidated. To determine the question of the 
validity of the patents two suits were brought against the H. K. 
Mulford Company in 1905, involving these questions: First, Are 
Adrin and Adrin Solutions infringements of the patents covering 
Adrenalin and AdrenaHn Solution, respectively? Second, If so, are 
these patents valid? Upward of five years was consumed in taking 
expert testimony respecting the history of the discovery, etc., and the 
hearing was not had until February 3, 191 1, when the matter was 
submitted on argument, the records and briefs covering over a 
thousand closely printed pages. 

Saturday, April 29th, Judge Hand, of the United States Circuit 
Court for the Southern District of New York, handed down an 
elaborate opinion answering both questions affirmatively. The effect 
of this opinion is that other substances similar to Adrenalin, and 
called by other names, are infringements of the Takamine patents. 

Concluding, Judge Hand says : 

" Whatever confusion the intricacy of the subject matter causes, 
one fact stands out which no one ought fairly to forget : Before 
Takamine's discovery the best experts were trying to get a prac- 
ticable form of the active principle. The uses of the gland were so 
great that it became a part of the usual therapy in the best form 
which was accessible. As soon as Takamine put out his discovery, 
other forms practically disappeared ; by that I do not mean abso- 



348 Correspondence Am. Phar. Asso. \^'^jiu'\m^''°' 

lutely, but that the enormous proportion of use now is of Takaniine's 
products. There has been no successful dispute as to that ; 
hardly, indeed, any dispute at all. What use remains is, so far as 
tlie evidence shows, of the old dried glands, which every one concedes 
to have been dangerous, at least for intravenous use. All this ought 
to count greatly for the validity of the patent, and Takamine has a 
great start, so to speak, from such facts. . . . He has been 
author of a valuable invention, and has succeeded where the most 
expert have failed." 

The litig"ation has been conducted in the most friendly spirit 
between the two great houses concerned. Parke, Davis & Co. had 
nothing to lose, since, had the patents been declared invalid, they 
would not longer have been handicapped by the payment of royalty, 
but could have marketed upon equal terms with competition. As it 
is, under their arrangement with Takamine, they are entitled to the 
exclusive right to manufacture and sell the active principle of the 
suprarenal gland, its salts and solutions, during the life of the 
patents, after which the Doctor's processes, as well as his products, 
will become puhlici juris. 



CORRESPONDENCE. 

american pharmaceutical association. 

Editor American Journal of Pharmacy : 

Enclosed please find an announcement of the preliminary 
arrangements for the approaching meeting of the A. Ph. A. 

Kindly use as much of it as you can give space for, and I will 
supplement this notice with more specific details as they are finally 
determined upon. 

Our members are enthusiastic and promise great things in the 
way of entertainment, and we are assured that the meeting will be 
a most successful one. 

Yours sincerely, 

C. Herbert Packard. 

THE AMERICAN PHARMACEUTICAL ASSOCIATION AT BOSTON, 
AUGUST 14 TO 18, I9II. 

The meeting of the American Pharmaceutical Association at 
Boston in August promises to be one of the most successful meetings 
in the history of this honorable scientific organization. 



^"'jSy^im*™ } Correspondence Am. Phar. Asso. 349 

Boston is an ideal city for a summer convention and the doors 
of her warm-hearted hospitaHty are being set wide-open to welcome 
with the most diligent service of heart and hand, her friends of the 
East, the West, the Southland and the Northland, whose smiling 
faces and cheery welcomes have so often made the Boston phar- 
macists feel at home with them. 

While Boston's welcome to the association will be a warm one, 
yet one need not think it attributable to the temperature, for Boston 
is never sultry ; the breezes from Massachusetts Bay, which are 
nearly always in evidence, making the city cool when places inland 
are sweltering in heat. 

Beyond the natural interest which the scientific pharmacist will 
have in the interesting and instructive meetings at which will be 
gathered the leaders of pharmaceutical thought of this and foreign 
countries, the other many and varied attractions of St. Botolph's 
town appeal to every one and draw them irresistibly to that city, 
for without the inspiring memories which throng around it, there 
would be no American pharmacy. Its streets were trod by Warren, 
by Adams, by Revere and by Hancock, and the first American blood 
shed for our independence flowed in its streets. Around and about 
the city are Lexington and Concord, Bunker Hill and Dorchester 
Heights ; Plymouth with its historic " Rock," where the Pilgrims 
established the first American Commonwealth, In the Name of 
God, Amen ! " ; Cambridge with its memories ; John Harvard and his 
college, with its treasures of surpassing interest in its Germanic 
Museum and other interesting collections, its reminiscences of Long- 
fellow and of Lowell ; Salem, the Witch City and its House of Seven 
Gables of Hawthorne ; Gloucester with its " Reef of Norman's 
Woe"; and Marblehead, through whose streets ''Old Floyd Ireson 
was carried in a cart" ; Amesbury and Haverhill with their memories 
of " The Quaker Poet," Whittier. 

Around Boston is an inexhaustible mine of history and memories 
among which the visitors to that city may delve for weeks to their 
interest and profit. 

The Committee on Entertainment, under the energetic lead of 
Mr. C. Herbert Packard, the Local Secretary, is working diligently 
to assure to every member in attendance a most pleasurable occasion, 
with the avowed purpose that all will ever remember it as an event 
in their lives. The co-operation of the Chamber of Commerce, an 
organization of 3000 leading business men of Greater Boston, has 



350 Book Reviews. { '^"'.hi?y,''i9n*""' 

been pledged, and its President, Mr. George S. Smith, will probable- 
welcome the association to the city ; Governor Foss and Mayor Fitz- 
gerald have both earnestly assured the committee of their desire to 
extend to the members a true Boston welcome. 

The headquarters of the association will be at the Hotel Vendome, 
one of the noted hotels of this continent, whose walls have sheltered 
royalties in their visits to Boston. This hotel is located on the 
famous Commonwealth Avenue, one of the finest residential avenues 
in the country; within a stone's throw of this hotel is the noble 
Copley Square, which is undeniably one of the finest public squares 
of the world, vying for pre-eminence with the Place de la Concorde 
in Paris. 

The meetings of the Association will be so arranged as to give 
abundant time for sight-seeing, and the ladies who accompany the 
members will be taken into the assiduous care of the Ladies' Enter- 
tainment Committee, of which Mrs. Adelaide Godding, the wife of 
the President-elect of the association, is chairman ; and it is therefore 
certain that not an idle or a tedious moment will be allowed to 
intrude its attention upon any of the fair visitors during their visit 
to the Hub. 

The Committee on Entertainment say that the old adage, " See 
Naples and die," has been recently revised and now reads, " See 
Boston and live ; enriched for all time with the memory of its 
treasures, and of its hearty New England welcome." 

Come to Boston ! ! ! 



BOOK REVIEWS. 

Organic Chemistry for the Laboratory. By W. A. Noyes, 
Ph.D., Professor of Chemistry in the University of Illinois. Second 
Edition, Revised and Enlarged. Easton, Pa., The Chemical Pub- 
lishing Company. 1911. 

Professor Noyes has well stated in his preface to the first edition 
of his Laboratory Manual " that " the science of organic chemistry 
rests, for its experimental foundation, on the preparation, usually 
by synthetic means, of pure compounds. Without a knowledge, 
based on personal experience in the laboratory, of the relations 
involved and the methods which may be used in such preparations, 
no satisfactory knowledge of the science can be acquired." 



Am. Jour. Pharm. | 
July, 1911. / 



Book Reviews. 



351 



The book has been well conceived and well developed, and it 
will not only be found useful to the student, but also of special value 
to the advanced worker, as it is full of suggestions. The most 
important laboratory processes which have been worked out in the 
development of organic chemistry are considered. The directions 
are full and accurate, and the theoretical explanations of the 
processes are clear and concise. 

In addition to much valuable information, as found in the chap- 
ters on the general operations, the analysis of carbon compounds, 
and the quahtative examination of such substances, the methods for 
the preparation of 131 separate compounds are given. These include 
hydrocarbons ; alcohols and phenols ; ethers ; aldehydes, ketones and 
their derivatives ; acids ; derivatives of acids ; hydroxy and ketonic 
acids; carbohydrates; halogen compounds; nitro compounds; 
amines ; diazo, hydrazo, nitroso and other nitrogen compounds ; and 
sulphur compounds. 

While this book has been prepared especially for the organic 
chemist, it will be found of very great service to the manufacturing 
pharmacist. Indeed, the pharmacist, who spends some of his time 
in the laboratory will be stimulated in his work, and will be well 
repaid if he adds to his desk library this new edition of Noyes's 
" Organic Chemistry for the Laboratory." 

The Fats. By J. B. Leathes, M'.A., M.B., F.R.C.S., Professor 
of Pathological Chemistry in the University of Toronto. Long- 
mans, Green & Co., London, New York, Bombay and Calcutta. 
1910. 4s. net. 

This is the eleventh of the series of monographs on " Biochem- 
istry " edited by Drs. Plimmer and Hopkins. These are exceed- 
ingly valuable books. Each monograph has been prepared by a 
specialist, and contains a complete bibliography. The contents of 
the present volume include: (i) the fatty acids, glycerol and the 
glycerides, other alcohols and their fatty acid esters, phospholipines, 
galactolipines and lipines ; (2) the extraction of fat, and the estima- 
tion of fat in animal tissues; (3) physical properties of fats, general 
chemical methods used in analysis of fats, separation, identification 
and constituents of fats : — fatty acids, alcohols and phospholipines ; 
(4) the physiology of fats : biochemical synthesis of fats and higher 
fatty acids, physiological oxidation of fats and the role of fats in 
vital phenomena. 



352 Book Reviews. { ^°\iub-'"i9ii*'"°" 

The book is especially intended for the use of physiologists and 
biochemists. It contains, however, much information that the dis- 
pensing pharmacist could use to advantage. In the making of oint- 
ments, the preparation of emulsions and the manufacture of sub- 
stances containing fatty constituents, he would obtain hints that 
would enable him better to co-operate with the physician and discern 
the objects he has in mind and why certain classes of fats apparently 
give more satisfactory results than others in given conditions. 

A Systematic Handbook of Volumetric Analysis or the 
quantitative determination of chemical substances by measure, 
applied to liquids, solids, and gases. By Francis Sutton, F.I.C, 
F.C.S., Public Analyst for the County of Norfolk, etc. Tenth 
Edition, revised throughout with numerous additions by W. Lin- 
colne Sutton, F.I.C, Public Analyst for the County of Suffolk, 
Norwich, Ipswich, etc., and Alfred E. Johnson, B.Sc, Lond. Phila- 
delphia: P. Blakiston's Son & Co., 191 1. $5.50 net. 

It is now nearly fifty years since the first edition of Sutton's 
" Volumetric Analysis " was published. This year the elder Sutton 
celebrates his jubilee as a Fellow of the Chemical Society, and well 
may the members rejoice with him in recognition of his achieve- 
ments and the useful work which he has done in pure and applied 
chemistry. Not only has Sutton's " Volumetric Analysis " been 
used by the pharmacist, manufacturing chemist, pathological chemist, 
etc., but it has also been adapted to the requirements in pure chem- 
ical research. And this may be taken to explain the secret of the 
success of the work. The author, having before him an ideal and 
being fully cognizant of the importance of research in advancing 
knowledge, has nevertheless utilized the results of research workers 
in the various fields of applied chemistry. 

It is indeed an inspiration to read the author's preface in this 
the tenth edition and find his enthusiasm unabated and his optimism 
as great apparently as in 1863, when the first edition came from the 
press. He says : " An exceptionally long interval of seven years has 
elapsed since the publication of the last edition of this work, whilst 
it has been out of print for nearly eighteen months, a fact which is 
without precedent in its history. The interval has not left me a 
younger man, and I must confess that as the time for a new edition 
approached I have found myself, at the age of four-score years, less 
equal to the task. So large and so constant is the work now being 



Am, Jour. Pharin. ) 
July, 1911. i 



Book Reviews. 



353 



done in the domain of volumetric analysis, that the need of recon- 
sideration of old methods and of selection from amongst the newer 
methods becomes more imperative with each succeeding edition of a 
book of this character. The present, moreover, being the tenth 
edition, I was particularly anxious that it should be distinguished 
by the most thorough and critical revision yet attempted, and, in 
the result, by the greatest possible consonance with modern practice. 
To this end, I placed its preparation entirely in the hands of my 
son and partner, W. Lincolne Sutton, who had accumulated a large 
amount of material in anticipation, and of Mr. Alfred E. Johnson, 
. . . who had rendered me valuable and acknowledged assistance 
in the course of preparing the ninth edition. I feel that I cannot 
pay too generous a tribute to the devotion of both editors to the 
task they tmdertook. ... I must admit that the result has 
rather damaged my conceit as an author, for it is obvious that many 
possible improvements will reveal themselves under a meticulate 
examination in a book which has grown, as this has, by a process 
of accretion tempered by pruning and extended through nine editions 
over a period of forty years. I am sensible that much remains to 
be done, but am sanguine enough to be looking forward already to 
the next and jubilee edition, when the book will have attained its 
fiftieth year." 

The editors have done their work exceedingly well. Much of the 
matter in the ninth edition has been entirely rewritten. It has been 
critically revised throughout, obsolete matter has been eliminated, 
but the general scope and original features of Sutton " are 
retained. For pharmacists who do analytical work this latest edition 
of Sutton's " Volumetric Analysis " will be indeed welcome. 

Materia Medica Step by Step. By Arthur W. Nunn, F.C.S. 
London: J. & A. Churchill; also P. Blakiston's Son & Co., Phila- 
delphia. 191T. $1.40 net. 

This is one of those books that a reviewer does not like to 
criticise. It is always unpleasant in commenting on a book " to 
damn with faint praise." But the impression on glancing at this 
book is not favorable. One or two illustrations will suffice to show 
this : The author says : 'TnuHn is a kind of starch. ... It 
can be distinguished from potato and other starches by the fact 
that when hydrolised it yields levulose, whereas the other starches 
when treated in the same way yield glucose." 



354 ^ook Reviezvs. { ^"' juTy,' 'ion*'"'"" 

Again, he says : ''Cellulose is another kind of starch. It . . . 
may be distinguished from starch by its resisting the action of 
potassium chlorate and nitric acid." 

But why call further attention to examples such as these? For 
him who uses the book it means " step by step " to failure. 



New and Non-official Remedies 191 i. Containing descrip- 
tions of the articles which have been accepted by the Council on 
Pharmacy and Chemistry of the American Medical Association, 
prior to January i, 191 1. Chicago: Press of the American Medical 
Association, 535 Dearborn Avenue. 1911. 

As stated by the Secretary of the Council in the preface, " The 
acceptance of the articles included in the book has been based in 
part on evidence supplied by the manufacturer or his agent, and in 
part on investigation made by or under the direction of the Council." 
Furthermore, we read : " The Council desires physicians to under- 
stand that the acceptance of an article does not necessarily mean a 
recommendation, but that so far as known it complies with the rules 
adopted by the Council." 

There are some ten official rules of the Council on Pharmacy 
and Chemistry of the A. M. A. The nature of them is probably best 
understood in their object. They have been adopted with the 
object of protecting the medical profession and the public against 
fraud, undesirable secrecy, and objectionable advertising in connec- 
tion with proprietary medicinal articles." It is not too much to say 
that the Council on Pharmacy and Chemistry of the A. M. A. has 
done for the cause of medicine what the Bureau of Chemistry of 
the U. S. Department of Agriculture has accomplished in the interest 
of pure foods. The Council has the support of the medical pro- 
fession in the same sense that the Bureau of Chemistry has the 
support of the members of that profession. The work of the Council 
is a most difficult and delicate one and yet a very necessary and 
fundamental one when we consider the almost bewildering number 
of compounds, many of which have absolutely no claim to merit, 
that are foisted on the medical profession each year. Some such 
course as this seems imperative if the profession in general would 
free itself from the stigma of quackery. To the younger prac- 
titioners the work of the Council should be especially helpful. Retail 
pharmacists generally must also appreciate the value of it and should 
procure copies of ''New and Non-official Remedies, 1911," which 



Am. Joui*. Pharm. 
July, 1911. 



Obituary. 



355 



may be obtained at a merely nominal charge by addressing the 
Secretary, Prof. W. A. Puckner, 535 Dearborn Avenue, Chicago, 111. 

Digest of Comments on the Pharmacopoeia of the United States 
of America and the National Formulary for the Calendar Year 
ending December 31, 1908. By Murray Gait Hotter and Martin 1. 
Wilbert. Washington: Government Printing Office. 191 1. 

Only the student who has experienced the grind of looking up 
the literature in connection with his investigations can appreciate to 
the fullest extent the value of the Digest of Comments." Up to 
within recent years, since the appearance of the first number of 
Digest of Comments/' the reviewer spent much time noting articles 
and conserving clippings of subjects he wished to keep informed 
concerning. This is all unnecessary now with articles pertaining to 
the Pharmacopoeia and National Formulary. It is very simple to 
take down the volumes of the " Digest of Comments " and quickly 
turn to the subject of the article one is working upon. There will 
be found, with abstract, references to all of the published papers on 
the subject during any one year. Not only this, but the foreign 
Pharmacopoeias are reviewed and valuable tables are given showing 
the relationship of the preparations in the dif¥erent pharmacopoeias. 



OBITUARY. 
Caleb R. Keeney. 

In the death of Caleb R. Keeney, the retail drug trade has lost 
one of the best types of the profession. Mr. Keeney was born in Car- 
lise, educated there, and apprenticed to the ist Henry Blair, who had 
his store where the 3d Henry C. Blair is now at Eighth and Walnut 
Streets, Philadelphia. 

Mr. Keeney at the termination of his apprenticeship commenced 
business for himself at Sixteenth and Arch Streets, and continued 
there until the day of his death ; his son having been associated with 
him for thirty-five years and succeeds to the business. 

There are not many drug pharniacists in Philadelphia to-day 
who have remained so close to the calling. He was what Prof. 
Parrish said a druggist was in liis neighborhood : An " Oracle " 
as it were. Tlie T*rofcssor in speaking of the druggist said that lie 



356 



Plianuaccntical Mce tii igs. 



Am. Jour. Pbarm 
July, 1911. 



was supposed to know everybody of any account in his section, and 
that the public found this generally to be true. I am sure that 
even to-day if one wishes to ascertain the residence of a person his 
first inquiry would be at the nearest drug store. Mr. Keeney saw 
many changes in his immediate section ; the old families vanished 
and new people came into the neighborhood. Other stores at times 
came into existence near him, but nothing could impair the confidence 
reposed in him and his store by his neighbors and the medical pro- 
fession. There is not a store in Philadelphia to-day where legitimate 
pharmacy is more in evidence than in the old store of Mr. Keeney. 
Living for a time near him and frequently dropping in I do not 
remember seeing a proprietary or many of those other rather incon- 
sistent items that most stores display. 

Mr. Keeney graduated from our College in the class of 1846 
and was at the time of his death the oldest living graduate. In the 
same class was the late Thomas S. Wiegand. He was a member of 
the College and for many years of the American Pharmaceutical 
Association. Of quiet tastes he w^on the esteem of all who were 
brought into contact with him, and it is gratifying to know that the 
pharmacy will no doubt be carried on in the same lines by his 
son, who has been with him for 35 years. He died February i, 
191 1, in his eighty-sixth year, after a short illness. He leaves a son 

E. T. Ellis. 



PHARMACEUTICAL MEETINGS. 

March meeeting. — The sixth of the pharmaceutical meetings 
was held on March 15, with W. L. ClifTe in the chair. At this 
meeting, two papers were read, treating of the subject of petrox 
preparations. The first of these papers was by Mr. Geo. M. 
Beringer, Ph.M., and George M. Beringer, Jr., P.D. This paper 
is the result of a rather extensive series of experiments which have 
been carried out by the authors in order to recommend the most 
satisfactory formulae for the petrox preparations of the National 
Formulary. A large number of preparations were shown and the 
entire paper is published in the May issue of this Journal. 

The paper by Mr. Raubenheimer is also published in this issue 
and was in the nature of a supplementary work to that of the pre- 



Am. Jour. Pharm. ) 

July, 1911. J 



Pharmaceutical Meetings. 



357 



ceding- paper, in fact the results obtained by Mr. Beringer and his 
son were confirmed by Mr. Raubenheimer (see p. 223). 

April Meeting. — The seventh of the pharmaceutical meetings 
was held on Tuesday, April i8th, with Dr. C. A. Weidemann in the 
chair. Professor C. B. Lowe gave an interesting talk upon Phar- 
maceutical Economics." He exhibited a number of pieces of appar- 
atus illustrating the making of emulsions, tablet triturates, fiUing of 
capsules, gelatin coating of pills, etc. He also called attention to a 
method which is sometimes useful in preventing the directions upon 
prescription bottles from becoming indistinguishable by reason of the 
liquid flowing on the outside when used by the patient. The directions 
are pasted next to the bottle and can readily be seen looking through 
the bottle from the opposite side. This is particularly useful in pre- 
serving the number of the prescription and the copy of the same. 
The number being helpful to the pharmacist and the copy useful to 
the physician. 

Professor Kraemer exhibited the collection of drugs of the 
Japanese Pharmacopoeia which he had received from one of the 
Honorary members of the College, Dr. W. N. Nagai of the Univer- 
sity of Tokyo. The specimens were in large glass stoppered bottles, 
made a splendid exhibit and included the following: Amylum 
Erythroni (Katakuri), obtained from Erythronium dens-canis L. ; 
Amylum Puerarise (Kazu) obtained from Pueraria Thunbergiana 
Benth. ; Radix Coptidis (Orea) Tamba, obtained from Coptis anemo- 
nccfolia S .et Z. ; Radix Coptidis (Oren) Kaga, obtained from Coptis 
Art; Radix Gentianse Scabrse (Riutan), obtained from Gentiana sca- 
bra Bge. uar. Buergeri Maxim.; Radix Phytolaccse (Shoriku) ob- 
tained from Phytolacca acinosa Roxb. var. esciilenta Maxim. ; Semen 
Pruni Armeniacse (Kiyonim) obtained from Prumis Armeniaca L. ; 
Folia Pruni Macrophyllse (Bakuchi yo) obtained from Primus 
macrophylla S. et Z. ; and Radix Taraxaci cum Herba (Hokoye) ob- 
tained from Taraxacum officinale Wigg. var glaucescens Kock. 

May Meeting.- — The last of the series of meetings for 1910 and 
1911 was held on May i6th, Mr. Henry C. Blair presiding. The 
meeting was given over to the members of the graduating class for 
the presentation and discussion of their theses. The following gave 
abstracts of the same : Morris Haimowitz, Samuel Millrood, Julius 
G. Rappaport, W. W. Rose and Frank X. Hedges. Abstracts of 
some of these theses will be published in later issues of this Journal. 



358 



Notes and News. 



J Am. Jour. Ptiarui. 
1 July, 1911. 



Notes and News. 
Prof. Oscar Oldberg received the honorary degree of Doctor 
of Laws at the commencement exercises of Northwestern University 
on June 14, 191 1. 

Samuel W. Fairchild, former president of the College of 
Pharmacy of the City of New York was awarded the honorary de- 
gree of Master of Science at the commencement exercises of Colum- 
bia University on June 27, 191 1. 

Prof. J. W. Sturm er of Purdue University was awarded the 
degree of Doctor in Pharmacy at the commencement exercises of 
Buffalo College of Pharmacy on June ist, 1911. 

Dr. Julian W. Baird, Dean of the Massachusetts College of 
Pharmacy, died on June 26, 191 1. Funeral services were held at 
the college building on June 28, 191 1. 

Prof. Harry Vin Arny, Dean of the Cleveland School of 
Pharmacy, has been appointed to the chair of Chemistry in the 
College of Pharmacy of the City of New York, succeeding Prof. 
Virgil Coblentz, who resigned to take charge of the analytical depart- 
ment of E. R. Squibb & Sons. 

Dr. E. F. Kelley, superintendent of the laboratories of Messrs. 
Sharp and Dohme, has become director of the Pharmaceutical 
Laboratory of the School of Pharmacy, University of Maryland. 

Prof. John Attfield, the eminent English chemist and one of 
the leading authorities in pharmaceutical chemistry, died on 
March 20, 191 1. A very complete biographical sketch qf Professor 
Attfield, written by F. A. Upsher Smith, was published in the 
March issue of this Journal for 1906. An excellent portrait of 
Professor Attfield also accompanies this article. 

Professor Attfield was " a man of many interests, and what- 
ever his hand found him to do he did that with all his might. And 
he did many things. He was one of the founders of the British 
Pharmaceutical Conference, for many years Editor of its Transac- 
tions, for 17 years its senior Secretary, and on two occasions its 
President. His connection with the British P'harmacopceia began 
in 1882 and ceased on the publication of the 1898 edition and the 
issue in 1900 of the Indian and Colonial Addendum." 

His body was cremated at Colder' s Green and in addition to 
the members of the family who attended the services, were a num- 
ber of representatives of societies with which Professor Attfield 
had a prominent connection. 



From photograph made by I'mlerwood and rnderuood, Xe\v ^'ork. 

HARVEY WASHINGTON WILEY 



THE AMEEIOAIf 

JOURNAL OF PHARMACY 



AUGUST, igii 



THE ESTIMATION OF MINUTE QUANTITIES OF 
NITROGLYCERIN.* 

' By Wilbur L. Scoville. 

From a medicinal point of view the estimation of nitroglycerin 
offers peculiar difficulties. This drug acts powerfully on the human 
system and is given in doses from i/iooo to 1/20 grain. The most 
common form of administration is in tablets, and a method of de- 
termining the strength of these with accuracy is much to be desired. 

For pharmaceutical purposes nitroglycerin is obtained in 10 per 
cent, alcoholic solution, which is practically a saturated solution, or 
in about 20 per cent, admixture with absorbent powders, as sugar 
of milk, chalk, talcum, etc., to which a little bicarbonate of sodium 
or carbonate of magnesium has been added for safety in shipping. 
There is evidence that both the solution and the powder-mixture 
deteriorate slowly. In cold weather a portion of the nitroglycerin 
will separate from the alcoholic solution, leaving the liquid weak 
unless the precaution is taken to warm and redissolve. Furthermore 
as L. H. Bernegua has pointed out ^ there is a loss in the process 
of manufacturing tablets of nitroglycerin, and the accuracy of the 
tablets is not therefore a question merely of mathematics and careful 
workmanship. 

For the estimation of nitroglycerin in pharmaceutical prepara- 
tions, two methods are in general use, — the nitrometer method, and 
titration after saponification with standard alcoholic potash. Of 
these the nitrometer method is undoubtedly the more accurate, and 

* Read at the Indianapolis meeting of the American Chemical Society, 
July. iQii. 

^ Amer. Jour. Pliar. 1907, page 555. 

(359) 



360 Estimation of Nitroglycerin. { au^II'^, lim!'"'' 

is probably the more used. For standardizing the stronger alcoholic 
solutions and the powder-mixtures (precautions being taken to ex- 
clude the carbonates present in the latter) it may give good results 
in skilled hands. 

But the nitrometer requires experience in its use, and par- 
ticularly for this substance. Newfield and Marx in an article on 
the use of the nitrometer- with special reference tO' the examination 
of nitrocellulose, a kindred body of nitroglycerin, — state that the 
sulphuric acid used must not be below 94.8% strength, the time of 
agitation not less than 3 minutes, and that the presence of other 
organic bodies may seriously afifect the results. They say that " a 
great number of details, some of them apparently trivial, affect 
the results to a considerable extent." If we add to these the difficulty 
of weighing accurately and transferring completely to a nitrometer, 
so viscid a substance as nitroglycerin, without unduly diluting it 
in the transferring, it is not to be wondered at that one unacquainted 
with all of these necessary details should obtain results varying 
from 82% to 108% in half a dozen assays on the same sample, and 
become discouraged thereby, although accustomed to the nitrometer 
in the assay of ethyl nitrite. Hence the statement often made that 
" experience is necessary " in the use of the nitrometer for nitro- 
glycerin assays, cannot be too strongly emphasized. 

Furthermore for the estimation in tablets there are additional 
difficulties. 

The method of estimating nitroglycerin by saponification with 
alcoholic potassium hydroxide has been proposed by several writers. 

Mr. Hay states ^ that the decomposition of nitroglycerin by 
alcoholic potash is of a complex nature, the products being potassium 
acetate, oxalate and formate, free ammonia, etc. Nevertheless he 
offers an equation wherein 5 molecules of potassium hydroxide act 
upon I molecule of nitroglycerin to give the above, and proposes 
that equation as the basis of assay by titration with standard alcoholic 
potash and standard acid. 

In 1895 Dr. Charles Rice recommended * the estimation of nitro- 
glycerin by saponification with standard potassium hydroxide and 
standard acid, on the basis that the reaction products are simply 
potassium nitrate and glycerin. The high position and reputation 

^ Jour. Anier. Chem. Soc, 1906, page 877. 

^ four. Chem, Soc, 1885, page 742. 

* Amer. Drug. & Pharm. Rec. July 10, 1895, page 6. 



Am. Jour. Pharm. ) 
August, 1911. ; 



Estimation of Nitroglycerin. 



361 



of Dr. Rice gave this process an immediate standing, and it has since 
been endorsed by several writers, notwithstanding that it was 
pointed out as early as 1868 by Tilberg ^ a Swedish chemist that the 
reaction between potassium hydroxide and nitroglycerin is not a 
simple but a very complex one, and results in nitrite, cyanide, 
oxalate and formate of potassium and free ammonia, and that in 
1885 Hay reiterated this fact. The endorsements of this process, 
as well as Dr. Rice's own experiments appear to be based on the 
fact that expected results are frequently obtained by it, but without 
any proof that expected results were correct results. 

In 19 10, Berl & Delpy ^ stated that when cold alcoholic solution 
of potassium hydroxide is mixed with nitroglycerin, and the tem- 
perature kept under 25° C. for some time, the products of reaction 
are potassiumi nitrate, nitrite, cyanide, oxalate, mesoxalate and 
formate, aldehyde, ammonia, glyceryl dinitrate and glyceryl trini- 
trate — (some of the last remaining undecomposed) . They further 
state that 6 molecules of potassium hydroxide are required to de- 
compose one of nitroglycerin and that the reaction is not complete 
in the cold. 

Here then there is one chemist (Hay) who says that one molecule 
of nitroglycerin requires 5 molecules of alkali, another (Rice) that 
3 molecules of alkali are required, and a third (Berl & Delpy) that 6 
molecules are necessary. 

And one has only to try the process, varying the conditions of 
heating, the time of standing, and the temperature, to become con- 
vinced that the results are of no value. 

Indeed one is surprised to note how much variation in results is 
induced by slight variations in the process. 

In 1905, Binz' a Swedish chemist proposed to estimate nitro- 
glycerin by saponifying it with alcoholic potash, reducing the nitrate, 
cyanide, etc., so formed to ammonia by treating the liquid with nascent 
hydrogen (formed by zinc and sulphuric acid added to the liquid) 
then estimating the ammonia, after distillation. In this process the 
nitrogen is first converted entirely into ammonia, and the latter 
estimated. This appears to be scientifically sound, and if conditious 
can be made to ensure complete reaction without loss of nitrogen 
in any form, it may give accurate results. The writer has not tried 

° Proc. A. Ph. A., 1869, page 242. 
Ber. 43 1421 thro. Chem. Al)st.. 1010—2488. 
Year Rook Pliarni., 1906, page 53. 



362 



Estimation of Nitroglycerin. 



< Am. Jour. Pharm. 
\ August, 1.911. 



it. It suggests the Kjeldahl method of estimating nitrogen, — which 
the writer has tried on nitroglycerin with good results. 

For pharmaceutical purposes the need applies particularly to an 
estimation of minute quantities, as in i/ioo grain tablets, etc. 

The writer first attempted tO' use " nitron " for this purpose but 
the insolubility of nitroglycerin in water makes this impracticable. 

The use of phenol disulphonic acid, as in water analysis for the 
estimation of nitrates, then suggested itself. On trial this worked 
well, and appeared to give excellent results. It then remained to 
ascertain whether such results were correct. 

Since this reagent must be applied to a dry residue, the first 
question relates to the volatility of nitroglycerin, some writers hav- 
ing asserted that it is slightly volatile. 

A (supposedly) 10% alcoholic solution was evaporated under 
three conditions, two samples of 10 c.c. each being used for each 
test. 

No. I the alcohol was driven off on a steam bath, the residue 
being removed from the bath before the last traces of alcohol had 
disappeared, then dried in a vacuum desiccator. 

No. 2 was subjected to a blast of warm air until the alcohol had 
been dissipated, then dried in a vacuum desiccator. 

No. 3 was placed in a vacuum desiccator and the vacuum main- 
tained during 60 hours. 

The residues weighed : 

No. I A = 1.030 (b) = 1.029 Gm. 
No. 2 A= 1.0135 (b) = T.0115 Gm. 
No. 3 A= 1.027 (b) = 1.032 Gm. 

On subjecting some of these residues to a moderate heat, as on 
top of a steam-bath, above and removed from a steam-bath, on warm 
sand, etc., they all lost weight with varying rapidity, while residues 
which were maintained in a vacuum in the desiccator and weighed 
daily, lost only 1.5 and 1.6' milligrams in 6 days. It was further 
learned that when in evaporating the alcohol by aid of a very mod- 
erate heat — (40° to 50° C.) if the residue was left in the heat after 
the alcohol had disappeared, the results were lower and were uneven. 
It appears therefore that nitroglycerin is not volatili/:ed even in 
a vacunm in ordinary temperature but that dry nitroglycerin is 
slowly deco})iposed by a very moderate temperature. This sample of 
solution had a density of 0.8650 at 25° C. and tested by the Kjeldahl- 



Am. Jour. Pharm. ) 
August, 1911. ; 



Estimation of Nitroglycerin. 



363 



Gunning method gave 8.642, 8.717, 8.732 and 8.822 per cent, of 
glyceryl trinitrate, — average 8.72 per cent. w.v. The evaporation 
method therefore gives high, though uniform results. 

In operating the Kjeldahl-Gunning method there is trouble with 
frothing unless the alcohol is first driven ofif completely, a trouble- 
some matter to operate without loss in a Kjeldahl flask. The precau- 
tion must also be taken to entirely dissolve the nitroglycerin in the 
acid before heating, a matter which requires a thorough shaking and 
a little patience, but avoids subsequent loss by minute explosions. 

Tested by the phenoldisulphonic acid method this solution showed 
8.3 per cent, w.v., which, considering the minute quantity used for 
this test, is very satisfactory. 

Two other samples of the same order-lot of solution, but taken 
from different containers, were tested by the evaporation, Dumas, 
Kjeldahl-Gunning, and the colorimetric methods. The results follow : 

Solution No. 2. Spec. Grav. at 26° C. 0.8390. 

Evaporation method 5.91 per cent, and 5.84 per cent. w. v. 

Dumas (combustion) method 5.79 per cent. 5.85 and 5.84 per cent. w. v. 

Kjeldahl-Gunning 5.82 per cent. w. v. 

Solution No. 3. Spec. Grav. at 25° C. 0.8536. 

Evaporation method 8.83 and 8.85 per cent. w. v. 

Dumas (combustion) method 8.534 per cent, and 8.545 per cent. w.v. 

Kjeldahl-Gunning 8.42 per cent. w. v. 

From each of these, dilutions were made to contain i gram of 
nitroglycerin in loo c.c. of alcohol solution, at 20° C. calculated from 
the Dumas estimation, and these dilutions were tested by the colori- 
metric (phenoldisulphonic acid) method. Each of four solutions 
tested I gram in 100 c.c. colorimetrically. 

This method therefore gives as accurate results as a colorimetric 
method may, and for the estimation of minute quantities is greatly 
to be preferred. 

The method of a])plying the test is essentially the same as is used 
in water analysis. The standard solution of potassium nitrate was 
used as standard. This is made by dissolving 0.722 (0.7217) gram 
of pure fused potassium nitrate in sufficient water to make 1000 c.c. 
One c.c. of this solution contains 0.0001 gram nitrogen in the form 
of nitrate and 1.2 c.c. of this solution contains the same amount of 
nitrogen as i/ioo grain of pure nitroglycerin. Of the alcoholic 
solutions the equivalent of 0.00065 Gm. (or i/ioo grain) of pure 



364 Estimation of Nitroglycerin. { '^'";ug°"^; m?'"" 

nitroglycerin (calculated) was measured into a small porcelain 
evaporating dish, and allowed to evaporate spontaneously. Into 
another dish was measured 1.2 c.c. of the standard nitrate solution 
and evaporated at a low temperature. When both were dry 2 c.c. 
of the phenoldisulphonic acid reagent were added to each, the mixt- 
ure stirred well with a glass rod and allowed to stand 10 minutes, 
then diluted with water, rendered slightly alkaline with potassium 
hydroxide, cooled and diluted to 100 c.c. — or 200 mm. in the com- 
parison tubes. The colors were then compared in a Schreiner colori- 
meter in the usual way. 

If a colorimeter is not at hand, Nessler tubes will give very 
good satisfaction. In the colorimeter a difference of ^/oq or 5 per 
cent, is easily discerned. 

For tablets, five ^/^oo grain tablets are powdered, to c.c. of alcohol 
added and the mixture shaken frequently during i to 2 hours, then 
filtered. 

Two c.c. of the clear filtrate is then evaporated and treated. 
Other strength tablets are treated similarly, the equivalent of ^/loo 
grain being taken for test. If the tablets are easily friable they are 
broken up with a glass rod after adding the alcohol. 

The test, so far as tablets are concerned was proven by adding a 
known alcoholic solution of nitroglycerin to varying quantities of 
sugar of milk, drying without heat then treating with alcohol as 
above and applying the test. The full amount of nitroglycerin put 
in was recovered by the test, except in one instance when an exces- 
sive amount of sugar of milk was used. 

A sample of the U.S. P. Spirit of Nitroglycerin containing i per 
cent, by weight of nitroglycerin was made from' solution No. 3. 

The specific gravity of this at 25° C. is 0.81378. Ten c.c. of it 
made a clear mixture with 12 c.c. of water at 15° C, but 13 c.c. at 
this temperature produced a marked milkiness. 

The present U.S. P. tests on this spirit allow so wide a range 
as to be of little value. The above sample has been kept six months 
and shows no change in strength. 



Am. Jour. Pliarni.') 
August, 1911. / 



Digitalis Hairs. 



365 



VARIATIONS IN THE FORMS OF DIGITALIS HAIRS.^ 

By Henry Kraemer. 

While considerable attention has been given in a general way to 
the pharmacognosy of digitalis, these studies have for the most part 
aimed to differentiate digitalis from other leaf drugs which may 
have been occasionally substituted for the genuine drug. As a 
matter of fact the adulteration of this drug or its substitution is 
very rare indeed. When we consider that digitalis has been used 
in medicine for some 400 years and see the conflicting statements 
that are still made regarding the efficiency and deterioration of the 
drug and its preparations, we may well ask how much progress 
has been made in the solution of the problems which this drug 
with its complex constituents presents. It is true that we have 
methods for the biological standardization of the drug and its 
preparations but these do not enable us tO' determine in advance 
which lot of drug will, in a given instance, be found valuable and 
which will be of inferior quality. It is not toO' much to claim that 
no work on such an important drug as this will be complete 
until we can determine either by chemical analysis or through phar- 
macognostical studies the dift'erences between different samples 
of drug. One thing that is needed, then, owing to the complexity 
of the chemical constituents, is more or less extended work in con- 
junction with pharmacological tests having in view a closer dif- 
ferentiation of the physical and mdcroscopical characters of the 
specimens examined. It is true that we have in the various phar- 
macopoeias such statements as, that the leaves only of the second- 
year plant shall be used, and at the present time there is a ten- 
dency to require that the leaves shall be thoroughly dried and kept 
in containers with freshly burnt lime. But we find that recent 
investigations tend to show that the leaves of the second-year 
plant are relatively but slightly more potent. And again, we know 
that certain practitioners use only the tincture of the fresh drug. 
Furthermore, there is a tendency in many quarters in spite of the 
restrictions in many pharmacopoeias that the leaves only of wild 
plants shall be used, to employ the leaves of cultivated plants, and 

^ Presented at a meeting of the Pennsylvania Pharmaceutical Association, 
June, 1911. 



366 



Digitalis Hairs. 



( Am. Jour. Pharm. 

I AugU6t, 1911. 



this is the practice of many discriminating pharmacists in the 
United States. 

Of all the papers which have been published on digitalis, the 
one by Hartwich and Bohny ^ seems to me to be the most impor- 
tant from a pharmacognostical standpoint. The whole work is of 
a basic character and sets forth many observations showing varia- 
tion in the structure of wild plants and those selected from culti- 
vated varieties. These authors point out that among other things 
that the leaves of wild digitalis are usually more hairy, that the 
cells of the hairs are shorter and broader and that the cuticle, or 
outer walls, of the middle and lower cells of the non-glandular hairs 
are finely papillose. Vogl - has called attention to the fact that 
the end cells are occasionally either fine striated or slightly papillose. 
As a matter of fact the observations of both of these authors are 
correct. In regard to the number of cells making up these non- 
glandular hairs, Vogl states that they are mostly 3-celled, Hart- 
wich and Bohny state that they are usually 2- to 4-celled and seldom 
5- to 6-celled, and Greenish ^ records the fact that exceptionally 
they may be as many as ten cells long. While I have not been able 
to confirm Greenish's observation, I have seen specimens in which 
many of the hairs were 7 to 8 cells long, and I believe that his 
statement can be confirmed. Most authors agree that the head 
or glandular portion of the glandular hair consists oi one or 
two cells but Hartwich and Bohny state that they are seldom i- 
or 4-celled. The stalks of these glandular hairs are usually i- or 
2-celled. A most interesting observation is recorded by Hartwich 
and Bohny that in between the veins occur long glandular hairs 
with usually a 4-celled stalk and a i -celled glandular head. These 
observations are all of the very greatest interest and should be 
borne in mind by students and practical workers in pharmacognosy. 

The entire leaf of digitalis is very characteristic, being more 
or less elliptical and the lower portion extending into the petiole 
(Fig. i). The margin is irregularly crenate but the most char- 
acteristic feature is the venation. From the central vein extend a 
number of prominent veins of the first order that diverge at angles 
of twenty to forty-five degrees, which serves to distinguish it 
from inula, in which the angles between the primary veins and 
the mid-rib are from sixty-five to nearly eighty degrees. The vena- 
tion at the teeth is also considered by many authors * to be rather 
characteristic for digitalis. While the comimercial drug will yield 



Am. Jour. Pharin. 
August, 1911. 



Digitalis Hairs. 



367 



in some instances nearly entire leaves it is for the most part made 
up of broken fragments and the microscopical study of these frag- 
ments is of the very greatest interest. There are a number of 



Fig. I. 




Digitalis: A, a typical leaf showing the winged or laminate petiole and the veins of the first 
order which diverge from the mid-vein at very acute angles. B, transverse section of portion 
of leaf showing the separated or additional epidermal layer (S); epidermal layer (E); glandular 
hair (G); non-glandular hair {N); coUenchyma (6^). C, transverse section near one of the veins 
showing considerable of the separated or extra epidermal layer (5); with two non-glandular 
hairs (A^) and glandular hair (G)\ epidermal layer (E); lower epidermis {LE)\ chlorophyll 
layer {N) ; upper epidermis (UE)\ trachea; or vessels {T). 

characters in the anatomy of this leaf that might be studied, but I 
desire at this time to call attention oiily to certain variations of the 
hairs observed in different specimens, of the commercial drug as 
also of the cultivated plants. It is well known that in the hairs 



368 



Digitalis Hairs. 



( Am. Jour. Pharm. 
I August, 1911. 



of many plants active principles are contained. For instance the 
volatile oils yielded by the Labiatse are found in the glandular hairs 
of the plants comprising this family. The stinging hairs of the 
nettles are peculiar in structure and while of a non-g-landular char- 



FlG. 2. 




Transverse section of digitalis leaf, through one of the veins: UE, ui^per epidermis; P, 
chlorenchyma (mesophyll), containing chloroplastids; LE, lower epidermis; G, glandular hairs 
jV, non-glandular hairs; C, coUenchyma; tracheae or vessels; S, leptome or sieve. 



acter yet they contain irritating substances. Nothing appears to 
be known with regard to the nature of the secretory substances in 
the hairs in digitalis yet the fact that in certain specimens we find 
a preponderance of glandular hairs is suggestive that whether these 
substances are toxic or not or have any influence upon the action 



Am. Jour. Pharm. "j 
August, 1911. j 



Digitalis Hairs. 



369 



of the cardiac substances it may be that the minute study of the 
hairs will throw some light on the variation in the drug. 

As has been already stated there are twO' general types of hairs 
in digitalis, (i) non-glandular; (2) glandular. Usually the former 



Fig. 3. 




Various forms of hairs ot digitalis: A, vai'ious forms of apical cells; B. long stalked glandular 
hairs very common in leaves of cultivated plants; C, various non-glandular hairs showing 
crooked or bent apical cells; D, various forms of glandular hairs with short stalks. 



occur in greatest number but the reverse is frequently the case, 
especially in cultivated garden varieties. In fact I have seen in 
certain instances the glandular hairs so numerous that I was inclined 
to think tliat the observations previously reported and the illustra- 
tions made were erroneous. The non-glandular hairs are usually 



370 



Digitalis Hairs. 



f Am. Jour. Pbarm. 
\ August, 1911. 



2- to 5-celled and vary in length from 145/x to 435/x. The cells are 
quite slender, being 9 to 13 times as long as broad. In other cases 
they are much shorter and broader, being twice as long as broad. The 
apex is usually obtuse or slightly rounded, and seldom acute. (Fig. 
3, A.) In some specimens the end cell is characteristically curved or 
crooked (Fig. 3, C). Again the end cells of these long hairs may be 
nearly spherical and of a glandular character (Fig. 3, B). 

The glandular hairs in the crude drug found on the market 
usually possess a short i -celled stalk and a globular glandular head 
consisting of one or two cells (Fig. 3, D). In some specimens these 
are relatively few, or wanting entirely, while in other speci- 
mens they are quite numerous, being about 25 to the square milli- 
meter. The greatest interest is in the long-stalked glandular hairs 
(Fig. 3, B), which, in some specimens of leaves from cultivated 
plants, largely replace the long non-glandular hairs. One may 
count upon a single cross-section about one half millimeter long, 
one complete non-glandular hair ; three long-stalked glandular hairs ; 
the basal cells only of nine hairs, and eleven short-stalked glandular 
hairs. The impression that one receives from seeing slides of this 
character is that the hairs of digitalis are chiefly of the glandular 
type. 

One of the most unusual characters which has been observed 
in certain specimens of crude drug, has been the formation of an 
extra epidermal layer. It would be interesting to know the potency 
of preparations made from a drug of this kind. In presenting this 
paper at this time I have done so in order to call attention tO' the 
fact that the pharmacognostical study of this drug has by no means 
been exhausted. What is probably needed here is some statistical 
work in regard to the occurrence of the several types of hairs and 
their relative distribution in different specimens of the drug the 
pharmacological efficiency of which is being determined. 

LITERATURE CITED. 

' C. Hartwich and P. Bohny : Apotheker Zeitung, 1906 (Vol. 21), pp. 231, 232. 
August V. Vogl : Kommentar zur achten Ausgabe der Osterreichischen 

Pharmakopoe, 1908, p. 91. 
^ Henry George Greenish: The Microscopical Examination of Foods and 

Drugs, 1910, p. 136. 
*A. Tschirch and O. Oesterle : Anatomischer Atlas der Pharmakognosie 

und Nahrungsmittelkunde, Lief. 15, p. 319. 



Am. Jour. Pharm.J 
August, lyii. ( 



Preparation of Salvarsan. 



371 



THE PREPARATION OF NEUTRAL SUSPENSION OF 
SALVARSAN/ 

By George M. Beringer, Jr. 

The directions for preparing the neutral suspension of salvarsan, 
as given in the Hterature accompanying the product, are, apparently, 
very simple and require but little time for carrying out ; but therein 
lies a trap. The modified method given herewith has been found 
to yield a satisfactory product. 

The apparatus and material required are very simple. There 
will be needed: 

One or two beaker glasses (25 or 30 c.c), 

One cyHndrical measure (10 c.c), 

Two thin glass rods with rounded ends, 

One glass mortar (30 or 60 c.c), 

Three pipettes made from tubing of small diameter. 

One or two ampoules (5 or 10 c.c capacity). 

One funnel with slender stem. 
It has been found advantageous to keep these in a seamless tin 
box with tightly fitting lid. This is sterilized in a gas oven at a 
temperature of 200° C. for fifteen minutes and allowed to cool before 
using. 

In addition, the following should be prepared, in previously 
sterilized containers : 
50 c.c. 15 per cent, solution sodium hydroxide (in glass-stoppered 
bottle), 

25 c.c. solution hydrochloric acid (i part diluted HQ, 3 parts 

sterile water, in glass-stoppered bottle), 
200 c.c distilled water (contained in a flask and sterilized by boiling 

for 15 minutes), 
Phenolphthalein test paper. 

Salvarsan is sent into the market in sealed ampoules containing 
.6 Gm. The entire amount is generally made into suspension, the 
physician dividing the dose, if need be, when administering. It is, 
as you are probably aware, in the form of a hydrochloride. This is 
readily hydrolyzed by water, so that aqueous solutions contain free 
acid, which makes them objectionable for injection. While it is 



^ Read at tlic meeting of tlie New Jersey Pharmiacetitical Association, 
June 14, 1911. 



372 Preparation of Salvarsan. {"^'aiS' rJiT™' 

soluble in alkaline solutions, they are exceedingly paniful when 
injected; hence the need for a neutral suspension of the base itself. 

The material having been prepared, as previously directed, the 
ampoule containing the drug is washed with w^ater and, finally, with 
alcohol. This is necessary because they are generally badly smeared 
with glue. The ampoule is then opened and emptied immediately 
into the mortar. Fifteen or sixteen drops of the soda solution are 
added and mixed with the material. Then enough distilled water is 
added, drop by drop, to make a moderately thin paste. Great care 
must be taken, from this point to the end of the preparation, to 
thoroughly triturate the material. Every particle must be rubbed 
till a smooth, creamy mixture results. It is now to be tested for 
alkalinity by applying a small portion of the mixture, by means of one 
of the rods, to a piece of phenolphthalein paper. If not faintly alka- 
line add soda solution, drop by drop, with continued trituration, till 
it gives the reaction, adding sterile water, from time to time, if the 
preparation becomes too thick. Now the HCl solution is added, drop 
by drop, till the mixture just ceases to react upon the test paper. 
Great care must be taken to rub up any cheesy lumps that may form 
when the acid is added. More water is added and the mixture 
transferred to the graduated cylinder. The portions of the precipi- 
tate adhering to the sides of the mortar and the pestle are rinsed 
down with the aid of a glass rod and sterile water, dropped as 
needed, and added to that in the cylinder. Enough water is added 
to make the product measure 8 c.c. and the mixture transferred to 
the ampoule by means of the funnel. Two c.c. of water are now 
used to rinse the adhering material from the measure and funnel 
into the ampoule. The excess of stem is filed and broken from 
the ampoule, which is immediately sealed by a blow-pipe flame 
directed across the edge of the open tube till the glass is perfectly 
fused. After cooling, the container is shaken to insure mixing. 

Many physicians make the injection at two sites, using the 
suspension in portions of 5 c.c each. For this purpose, a beaker 
glass will be needed in dividing the preparation. An extra beaker 
is provided because the operator frequently has immediate need of 
an extra vessel of some kind in the midst of his work. 

It is better to have a large mortar than one too small, as the 
precipitate can be more easily rubbed smooth in the former. A 
porcelain dish as directed in the circulars is exceedingly unsatis- 
factory. 



Am. Jour. Eharm. ) 
August, 1911. J 



Action of the Enzymes.- 



373 



The hydrochloric acid is directed to be much more dilute than 
that originally used, as it has been found to give a lighter and a 
finer precipitate. 

The suspension should not be prepared long before it is to be 
used. At least an hour, however, should be allowed for its prepara- 
tion, and the operator should, under no circumstances, be hurried. 
The services of an assistant to handle the pipettes will materially 
shorten the time required. 

Phenolphthalein paper is much more certain in determining the 
reaction than litmus. Red litmus does not change till a great excess 
of alkali has been added. Blue Htmus is more sensitive but not so 
sharp in distinction as phenolphthalein. When neutral to the latter, 
the preparation slightly deepens the color of blue litmus. This seems 
to be the proper end point," as, when more acid is added till just 
neutral to litmus, the suspension of the precipitate is not so perfect. 



SOME THOUGHTS ON THE ACTION OF THE ENZYMES, 
WITH SPECIAL REFERENCE TO THE NATURE 
OF PEPSIN.^ 

By James E. Hancock. 

Ever since the discovery of the enzymes, physiological chemists 
have tried to explain the transformations that occur under their 
influences and to systematically reason why these changes should be. 
One theory and then another has been suggested, each of which has 
been based upon certain peculiarity of reaction that has happened 
under the particular investigator's notice. The study is fascinating 
because metabolism generally is a physiological process that cannot 
be even approximately understood until the actions of enzymes are 
comprehended. Every problem in the growth and dissolution of 
plants and animals, and especially in the transferences of energy, 
is connected in some way or other with the action of enzymes. 
Plants, with very few exceptions, acquire their food from the soil 
and from the air. By the action of enzymes under favorable in- 
fluences of light, heat and moisture, the organic materials that are 
thus absorbed are elaborated into complex compounds, consisting 



* Read at a meeting of the Maryland Pharmaceutical Association, June, 
1911. 



374 



'Action of the Enzymes. 



fAm. Jour. Pharm. 
Augii8t, lyii.i 



mostly of carbon, hydrogen, oxygen and nitrogen, and build up 
within themselves the sugars and vegetable proteids, which in turn 
are so necessary for the growth and maintenance of the animal 
kingdom. For a long time it was believed that all proteids were 
the products of vegetable life, but when the differences between the 
various complex albumins were studied, it was seen that the albumins 
found in animals were diff'erent from the albumins found in plants, 
and it is now known that no matter from what source the animal 
takes its food, the proteids have to be catalyzed before they are 
fit for its economy. 

Digestion in itself is an extremely simple word, but it is very 
comprehensive, and few realize how much is included in the process. 
Some authorities consider enzyme actions as a part of the vital proc- 
esses themselves, but others evidently cannot see beyond the ma- 
terial reactions that occur, until even in these days of advanced 
science no acceptable agreement is absolutely settled upon. The 
subject is necessarily a theoretical, indeed an obscure inquiry. In 
recent years a dynamic conception of the powers seems to be more 
and more acceptable and at least two advocates of such explanation 
would appear to approximate a reasonable theory for these processes. 
Naegeli assumes that catalysis is induced by vibratory action, and, 
apropos, it might be well to remind you that it is a generally 
accepted hypothesis to consider that the atoms of every molecule 
of matter are never at rest, but that they vibrate in a state of 
equilibrium which is consistent to the maintenance of its specific 
whole. It is supposed that the catalyzing agent — the enzyme — 
coming in contact with a body favorable to its action, communicates 
the vibrations of its atoms to the atoms of the molecules of the 
body that is being digested and breaks down their staple tension with 
a natural reduction of its complexes into other and simpler com- 
pounds. To get a better appreciation of what this atomic rearrange- 
ment may mean, we must remember that Grubler has estimated 
that the molecular weight of vitellin was 8848, from which was de- 
duced the formula C092H481NJJ0O83S2, and that Sabanejeff has de- 
termined that the molecular weight of ovalbumin was 15,000. The 
atomic rearrangement in the changes that might occur in such com- 
plexes, especially if modified or interfered with by external factors 
and inequalities would suggest a procession of geometric possibilities. 
The dynamic law of Laplace and Berthollet " That an atom or mole- 
cule put in motion by any power whatever may communicate its own 



Am. Jour, Pharm. ) 
•August, 1911. j 



Action of the Enzymes. 



375 



motion to another atom or molecule in contact with it," would thus 
seem to acquire a special significance in the biochemistry of the 
enzymes and might account for the many catalyses and syntheses 
that occur in our own bodies and in growing plants and animals, 
under the actions of enzymes when influenced by the sun's rays and 
other favorable conditions. Ostwald's generalization practically im- 
plies the same character of action when he states that these changes 
are brought about by the increased activity of molecular movement. 

Accepting either or both of these theories, even with modifica- 
tions, they at least reconcile the transformations that may occur in 
the phenomena of digestion as a peculiar quality of the enzymes, the 
smallest particles of which may be assumed as being in a state of 
motion, a state which is communicated to the atoms of the material 
that is being digested and with which they are in contact, thereby 
causing the atoms of the molecules of this matter to change their 
position and rearrange themselves in new groupings. Supplement 
this induced rearrangement with the processes of either oxidation or 
hydration, dependent of course on the peculiar quality of the par- 
ticular enzyme, and then carry this conception a little further and 
infer the action of disturbing external factors like heat or light, 
which are vibratory in their communications, — for it is entirely 
possible that the waves from these may intensify or abnor- 
malize this existing process, — and the products that are thus 
formed must necessarily alter with the temperature and the 
other modifications of transformation in which the enzyme works, 
because the changes in the newer bodies are the result of these 
imparted energies and the atomic rearrangement that is thus brought 
about must stand in particular relation to the manner of the actions. 
During the past winter my attention was called to an auto-digestion 
of pepsin that could only be reconciled by this reasoning, and an 
experimentation of several months with recurring resultants under 
similar conditions has been an interesting problem. As we all 
know, pepsin is an extremely sensitive body, and the best chemists 
have never been able to analyze it. We all know it is a soluble, 
unorganized ferment that differs in its mode of action from living 
ferments such as yeast apd bacteria, in that it possesses no power of 
self-nutrition and multiplication. Like all other animal extracts it 
is surrounded by the limitations that nature has placed upon it. 
It will bear an exposure to a prolonged low temperature without 
being injured, and it is active only in weak acid solutions, and then 



376 



Action of the Enzymes. 



f Am. Jour. Pharm. 
( August, 1911. 



when accompanied by two conditions — the presence of water and 
heat. Nature's economy provides that it shah be physiologically 
active at and about ioo° while an exposure of its simple solution 
to a temperature of 130° F. will quickly destroy its proteolytic activ- 
ity. Moreover, its digestive activity is always dependent on the 
medium in which it is exhibited. The U.S. P. requires that one grain 
of pepsin shall be able to digest 3000 grs. of coagulated egg albumin 
when suspended in a 0.2 per cent. HCl solution with water. By 
repurification this standard may be increased to a much higher 
potency ; but even in the highest degree of purification that it has 
yet been obtained, it is at least in combination with nucleo-proteid 
bodies. These nucleo-proteids are combinations of nucleic acid with 
albumin. Recently several authorities have advanced the theory 
that the nucleo-proteids themselves are the enzymes. This is espe- 
cially urged by Haliburton, and Pekelharing has practically arrived 
at the same conclusion and suggests that the nucleo-proteid is proba- 
bly the zymogen of the enzyme. This hypothesis is strengthened 
by the observations of McCallum, who showed that in nature the 
nucleus initiates the process of secretion and excretes some material 
into the cytoplasm which then undergoes further changes and ulti- 
mately enters into the zymogen, if indeed it does not actually 
form the principal part of it. Nencki and Sieber also state that 
pepsin contains nucleo-proteid and conclude that the zymogen — 
pepsinogen — is converted into pepsin by combining with the nucleo- 
proteid of the cell. The practical results of pepsin digestion of 
nucleo-proteids have been frequently demonstrated. Although they 
are much more resistant to hydrolysis than the true albumins, 
nevertheless under a prolonged peptic digestion, the nucleo- 
proteids are split into nucleins, being new compounds of nucleinic 
acid and protein fractions. 

A series of experiments in which pepsin and its natural asso- 
ciates were the only possible albuminous quantity present, in an 
acidulated solution under the action of heat and electric light for ten 
days, have given the following results : A precipitation of modified 
nuclein that is insoluble in the acid medium and a propeptone 
moiety that remains dissolved in the solution. I wish that I 
were prepared at this time to give you the ultimate results, but 
certain conditions will not permit. The purpose of this paper is 
only to urge that pepsin solutions should be kept in a cool, dark 
place, because of their sensitiveness to heat and light. 



''""Au^S;mL°''} ^ ^^^^ Vegetable Adulterant. 377 



A NEW VEGETABLE ADULTERANT. 
(outer layers of the pericarp of the fruit of juglans 

REGIA L.) 

By Henry Kraemer. 

At the Pharmaceutical Meeting of the Philadelphia Colleige of 
Pharmacy held November 16, 1909, Mr. E. H. Gane exhibited a 
sample of " vegetable shells/' which he stated were imported pro- 
bably for the purpose of replacing walnut shells, olive pits, etc., 
owing to the ease with which these latter products can now be 
detected when used as adulterants. (See Am. Jour. Pharm., 81, 
p. 597, December, 1909.) 

A preliminary examination of the sample showed that it was 
composed of the pericarp of some fruit. I then gave the sample 
to one of my students, Mr. Peter Amsterdam, tO' study micro- 
scopically and in comparison with the pericarps of similar fruits 
in our collection. This study showed that the material consisted 
of the hulls, or outer layers of the pericarp, of the fruit of Juglans 
regia, or English walnut, the nuts of which are common in the 
markets as an article of food. 

The hulls (outer portion of the pericarp) of the fruit of Juglans 
regia have been used in the fresh and green condition in medicine, 
and are described in foreign works imder the name of Cortex Fruc- 
tus Juglandis {Cortex nucum Juglandis viridis. Griine Walnuss- 
schalen. Brou de noix). The hulls are described by Vogl in his 
Pharmaco^gnosy, and a rather extensive article on their histology 
is given by Hartwich in the Archiv dcr Pharmacie, 66, p. 325 

(1887). 

Macroscopic Characters. — The dried hulls, or shells," consist 
of pieces or fragments composed for the most part of the outer 
layers of the pericarp, i.e., the epicarp and sarcocarp. The pieces 
are more or less irregular, involuted, shrivelled, vary from 5 to 35 
mm. in diameter, and break with a short fracture. Some of the 
pieces are marked by the stem-scar or still have attached to them 
portions of the stem. Externally, the epicarp, or outer layer, is 
rather smooth, though coarsely wrinkled, marked by numerous 
small dots, and varies in color from light to dark brown. The sar- 
cocarp, or inner layer, is somewhat spongy, dark brown or black- 



378 A New Vegetable Adulterant. { ^""Xu^^t" FJil""' 

ish- brown in color, and more or less fibrous, due to the shrink- 
ling of the parenchyma from the librovascular bundles. 

The taste of the hull is markedly acid and somewhat bitterish, 
but the odor is not very pronounced or characteristic. 

Microscopic Characters. — The epicarp shows the presence of 
numerous broadly elliptical stomata (Fig. A) which are from 50 
to 70 microns in length; the opening between the guard-cells is 
large, and sometimes irregular in outline, or the guard cells may be 
separated along the adjoining walls, due to the unequal development 
of the tissues. The blackish-brown spots, which mark the outer 
surface of the epicarp are made up of tannin-containing cells 
which appear to be under the influence of a local stimulus of some 
kind, the area affected being 0.2 or 0.3 mm. in diameter. The 
epidermal cells are more or less polygonal, the cuticle being from 
2 to 5 microns thick (Fig. B, e). Beneath the epidermis are two to 
three rows of tabular cells, usually containing a reddish-brown or 
tannin-containing sap (Fig. B, c) ; beneath these sub-epidermal 
cells is a continuous ring or zone (Fig. B, s) made up of three 
or four layers of stone cells, the walls of which are strongly ligni- 
fied, lamellated, and finely porous. The cells vary from tabular to 
irregular, and may or may not contain a reddish-brown tannin- 
like substance, the tannin being in the cells of the specialized 
areas already described. 

Beneath this zone of stone cells occur the tissues of the sarco- 
carp proper (Fig. B, p). This portion consists of parenchyma and 
fibro-vascular tissue. The cells of the parenchyma contain small 
starch grains and occasionally rosette aggregates of calcium oxalate 
which vary in diameter from 25 to 40 microns, and sometimes may 
be found in large numbers in the parenchyma cells adjoining the 
fibrovascular bundles. 

The parenchyma cells of the sarcocarp of the young fruits have 
very thin walls, but in the older fruits the walls of very many 
of the cells become lignified and have large oblique pores. The 
tracheae are in radial row^s two cells wide separated by medullary 
rays one cell wide. They are usually spiral. 

At both the apical and basal portions of the fruit occur curved, 
spear-shaped, unicellular, non-glandular hairs (Fig. D) re- 
sembling those found in the pericarp of the cereal grains, 
but distinguished from the latter by the fact that they 
are frequently united to form stellate groups resembling 



Am. Jour. Pharm. 
August, 1911. 



A New Ves:etahle Adulterant. 



379 



those of kaniala and those occurring- on the leaves of 
hamiamelis. The contents may be nearly colorless or con- 
sist of a reddish-brown tannin-like substance. There are also 



Fig. I. 




Pericarp of fruit of Juglans regia : A, stomata of epicarp; B, cross-section of pericarp; 
showing epidermis {e) , cells with reddish-brown contents (c), sclerotic cells (i), parenchyma (p), 
containing protoplasm and starch grains; C, mestome strand of the sarcocarp showing vessels 
iv), libriform (e), leptome (5), parenchyma containing protoplasm and starch Cp) ; D, non-gland- 
ular hairs from fthe apical and basal portions of fruit; E, glandular hairs from base of fruit 
similar to those found in large numbers on the surface of the butternut {Juglans cmerea); F, 
rosette-aggregates resembling the membrane crystals of Rosanoff ; G, sclerotic cells found in the 
powder; /f, fragment of non-glandular hair; A", starch grains from 2 to 10 u in diameter; L, 
tracheae with annular markings; M, calcium oxalate crystals. 



present, usually at the base of the fruit, and also on the stems, 
when these are present, long-stalked glandular .hairs (Fig. E) 
similar to those covering the fruit of Juglans cincrea (Butternut). 



38o 



A Nczv Vegetable Adulterant. 



f Am. Jour. Pharm. 
\ August, 1911, 



While the stalk is long and multicellular in the hairs of both species, 
the glandular head in the hairs of Juglans regia appears for the 
most part to consist of one or two cells, whereas in Juglans cinerea 
it is usually multicellular, resembling the glandular heads of the 
hairs of the Labiates. 

In the parenchyma cells of the basal portion of the hull there 
are a large number of rosette aggregates or spherites of crystals 
resembling crystals of calcium oxalate (Fig. F). These aggregates 
are more or less hollow, frequently attached to the cell-wall, some- 
times more or less enclosed by the cell-wall, and thus resemble 
the membrane crystals of Rosanoff (see Kraemer's Botany and 
Pharmacognosy, 4th ed., p. 171). These aggregates dififer from 
those found in the stem, which are the typical rosette aggregates 
of calcium oxalate, and are deserving of special study. 

Characteristics of the Powder. — The color is dark brown or 
blackish-brown, the odor faint, and the taste distinctly acid and 
slightly bitter. The most characteristic elements of the powder are 
the stone cells (Fig. G), some of which contain only air, thus 
resembling those of the olive pit, and some of which have a red- 
dish-brown content. There occur besides fragments of the stalks 
of the glandular hairs (Fig. D), fragments of the non-glandular 
hairs (Figs. D and H), small starch grains (Fig. K), the two 
types of rosette aggregates of calcium oxalate crystals (Figs. F and 
M), and large, thin-walled somewhat shrunken parenchyma cells, 
many of which contain either small starch grains or reddish-brown 
masses, or cells with rather thick walls having large simple pores 
and being more or less lignified, approaching stone cells. These 
latter sometimes contain the Rosanoff crystal aggregates already 
mentioned. 

When the hulls of Juglans regia are treated with water the 
solution soon shows a reddish-brown color which becomes much 
deeper on the addition of aqueous solutions of the alkalies. The 
aqueous extract of black pepper hulls, and black walnut shells 
(endocarp) has a color similar to that of the hulls of Juglans regia 
and behaves similarly toward solutions of the alkalies. The aqueous 
extract of pecan shells (endocarp) is of bright red or cherry red 
color, but becomes on the addition of alkalies of a dark reddish-brown 
color similar to that of the extract of the hulls of Juglans regia. 
Cloves give a reddish-yellow aqueous extract which becomes deep 
red on the addition of solutions of the alkalies. The aqueous ex- 



'^'^iuSmi''"'} Harvey Washing^ton Wiley. 381 

tracts of the following, are either nearly colorless or range from a 
pale yellow to a pale yellowish-red, or pale olive green ; and are not 
tnrned to a dark reddish-brown on the addition of alkalies : Black 
pepper, white pepper, Ceylon cinnamon, Cassia cinnamon, Saigon 
cinnamon, pimenta, ginger, English walnut shells (endocarp), olive 
endocarp (olive pits), peanut shells, Brazil nut shells (seed coat), 
and butternut shells (endocarp). 



HARVEY WASHINGTON WILEY. 

On Thursday, July 13th, the readers of the daily press were sur- 
prised to learn that the Committee on Personnel of the U. S. De- 
partment of Agriculture, consisting of Assistant Secretary Willet M. 
Hays, Solicitor George P. McCabe, and Chief Clerk C. C. Clark, had 
been " investigating a charge that Dr. Wiley and Dr. Kebler have 
exceeded their authority under the law in employing Dr. Rusby, 
and have recommended that Dr. Wiley be permitted to resign ; that 
Dr. Kebler be put in a place where he will no longer have power to 
make recommendations as to employment of experts, and that Dr. 
Rusby be dismissed." 

Scarcely anything short of an attack upon the country by a foreign 
foe could have so stirred the hearts of the American people generally. 
Dr. Wiley has published so many papers, has delivered so many 
public addresses, and has himself been the subject of so many inter- 
views, that he, as a matter of fact, has been in the limelight " 
continually. Furthermore, he is so genial, he is such a good speaker, 
he is so considerate of the welfare of the people that he may very 
properly be termed one of " America's leading citizens." Since the 
passage of the Federal Pure Food and Drugs Act he " has wielded 
more power than almost any other subordinate official of the Depart- 
ment of Agriculture. He was the prime mover in all the pure food 
legislation that has been enacted, and has been charged with the exe- 
cution of the law under the direction of the Secretary of Agriculture. 
Practically single-handed, he has waged a vigorous fight against the 
adulteration of foods entering into domestic and foreign commerce 
and has presented an uncompromising front to every attempt to 
evade or let down the strict letter of the law." 



382 



Harvey IVashington Wiley. 



( Am. Jour. Pharm. 
t August, 1911. 



To prepare a sketch of Dr. Wiley and his work would be to write 
a volume. Briefly then, Dr. Wiley was born on October i8, 1844, 
near Kent, Jefferson County, Indiana. In 1863 he entered the 
freshman class of Hanover College, graduating A.B. in 1867. En- 
tering upon the study of medicine in 1868, he graduated M.D. from 
the Indiana Medical College in 187 1. During his medical course 
he was instructor in Latin and Greek at Butler College. In 1872 
he entered the Lawrence School of Harvard University, graduating 
B.S. in 1873. He was Professor of Chemistry at Butler College in 
1873-4, and from 1874 to 1883 he filled the position of Professor 
of Chemistry at the Agricultural College of Indiana at Purdue. 
During this period he had leave of absence for the year 1878-79 
and studied in Germany. He was State Chemist of Indiana from 
1881 to 1883 ; was made Chief of the Division of Chemistry, 
U. S. Department of Agriculture in 1883, which position he held up 
to 1901, when he became Chief of the Bureau of Chemistry, which 
position he holds at the present time. 

The record of Dr. Wiley's connection with the evolution of the 
Federal Food and Drugs Law and legislation concerning Foods and 
Drugs in the United States, is, indeed, a stimulus to any young 
man with a laudable ambition. It is the successful record of a man 
with an ideal, who has worked indefatigably until his ideal became a 
reality. And, furthermore, like other men who have achieved great 
things for their countrymen, we find a cabal seeking to humiliate him. 
It is now just a quarter of a century ago that Dr. Wiley, as Chemist, 
submitted to Hon. N. J. Colman, then Commissioner of Agriculture, 
the first Bulletin (No. 13) on Foods and Food Adulterants. This 
Bulletin deals with dairy products only, but was rapidly followed by 
other detailed scientific studies on other products, as spices and condi- 
ments, fermented alcoholic beverages, lard, baking powders, sugar, 
molasses and syrups, tea and coffee, canned vegetables, cereals and 
preserved meats. At the very beginning Dr. Wiley realized that 
the support of the public who eat the food would be vital to the 
propaganda, for in 1889 submitted Bulletin 25 of the Bureau 
of Chemistry to the Hon. Jerry M. Rusk, then Secretary of Agri- 
culture, entitled " A Popular Treatise on the Extent and Character 
of Food Adulteration." In submitting this report by Special Agent 
Wedderburn, Dr. Wiley said : 

"The object of the present bulletin is wholly distinct from that pursued 
in Bulletin No. 13. The investigations, of which the present bulletin is the 



'*^"Au^ust mi'^'"" } Harvey Washington Wiley. 383 

result, were undertaken for the purpose of collating in popular form well 
authenticated facts respecting food adulteration, in order that the people 
and Congress might have at least a general view of the evil which it is 
hoped Mr. Wedderburn's work may help to remove." 

Mr. Wedderburn states in this Bulletin : " Enough will be found, 
I am convinced, in the pages of the following report to emphasize 
in the strongest manner the necessity for such national legislation 
as was sought during the last session of Congress by Messrs. Conger 
and Laird of the House Committee on Agriculture, as expressed in 
their very able report, as submitted to Congress by order of that 
committee." 

Some of the data in these pioneer reports are especially interest- 
ing in view of later developments. " Glucose is probably the lead- 
ing adulterant on the market. It is largely used in syrups, low- 
grade sugars, jellies, and cheap confections. Druggists, wholesale 
and retail, had none, but with singular unanimity referred the in- 
quirer to the candy manufacturers who, to a man, knew nothing 
of the commodity. Parenthetically, a specimen of taffy of another 
kind, abstracted from an inviting pile, yielded 79 per cent, of glucose 
on analysis." (Beckwith, Ohio State Board of Health.) Pickles, 
greened with sulphate of copper, adulterated spices, vinegars, canned 
foods, maple products, etc., all clamor in these pages for the 
attention that they have recently received in the notices of court 
judgments issued from the Department of Agriculture. 

One bill followed another, and in every Congress from the 
Fiftieth (1887) ^ iood bill was reported to each House. As 
chairman of the Committee on Legislation of the National Pure 
Food and Drug Congress, called in 1898, and as a witness every 
year before the Congressional committees considering these bills, 
Dr. Wiley has been indefatigable in his advocacy of pure food and 
drugs for the people, backing up his views with the scientific work of 
the Bureau of Chemistry on the one hand, and with popular edu- 
cation on the other. 

The study of imported foods was begun in 1898. Samples of 
a number of classes of foods were procured from the Custom officers 
at the various ports of entry and their quality and composition 
compared with similar food products purchased upon the open 
market alleged to be imported. The results were very interesting. 
On March 3, 1903, Congress in the Appropriation Act authorized 
the Bureau of Chemistry to supervise the importation of food 



384 



Harvey Washing^ton Wiley. 



( Am. Jour. Pbarm 
X August, 1911. 



products. This law became effective July i, 1903. The act author- 
izing this work reads as follows : 

" To investigate the adulteration, false labelling, or false branding of 
foods, drugs, beverages, condiments, and ingredients of such articles, when 
deemed by the Secretary of Agriculture advisable, and report the result in 
the bulletins of the Department; and the Secretary of Agriculture, when- 
ever he has reason to believe that such articles are being imported from 
foreign countries which are dangerous to the health of the people of the 
United States, or which shall be falsely labelled or branded, either as to their 
contents or as to the place of their manufacture or production, shall make a 
request upon the Secretary of the Treasury for samples from original 
packages of such articles for inspection and analysis, and the Secretary 
of the Treasury is hereby authorized to open such original packages and 
deliver specimens to the Secretary of Agriculture for the purpose mentioned, 
giving notice to the owner or consignee of such articles, who may be present 
and have the right to introduce testimony ; and the Secretary of the Treasury 
shall refuse delivery to the consignee of any such goods which the Secretary 
of Agriculture reports to him have been inspected and analyzed and found 
to be dangerous to health or falsely labelled or branded, either as to their 
contents or as to the place of their manufacture or production, or which 
are forbidden entry or to be sold, or are restricted in sale in the countries 
in which they are made or from which they are exported " (Sec- 
tion of Appropriation Act of March 3, 1905.) 

The same act provides for an investigation of food preservatives 
in the following language : 

" To enable the Secretary of Agriculture to investigate the character 
of proposed preservatives and coloring matters, to determine their relation 
to digestion and to health, and to establish the principles which should guide 
their use." 'I 

The results of the work were so satisfactory that laboratories 
were established in New York, San Francisco, Boston, Philadelphia, 
Chicago and New Orleans. 

The Federal Food and Drugs Act was passed on June 30, 1906, 
and became effective January i, 1907. The enforcement of this law 
was placed in the hands of the Bureau of Chemistry. Dr. Wiley 
was one of the three members of the special committee appointed to 
draw up regulations for the enforcement of the act. These regu- 
lations with minor changes in a few instances are still in force. 
Under this act the port laboratories referred to above remained in 
force, and numerous others were provided for at various ports of 
entry, as, for example, Savannah, Seattle, St. Louis, Detroit, etc. 
Thousands of foods and drugs have been examined under this act 



Am. Jour. Pharm. ( 
August, 1911. I 



Harvey Washington Wiley. 



38s 



and hundreds of successful prosecutions made. These prosecu- 
tions include some of the most flagrant frauds perpetrated on the 
public. For example, some of the so-called cancer cures, consump- 
tion cures, drug addiction cures, cocaine trafific, soothing syrups, etc. 
Dr. Wiley, through the drug division, has co-operated with the 
Post Office Department for the purpose of denying the privileges 
of the mails to numerous medicinal frauds, which is accomplished 
by the issuing of fraud orders by the Postmaster-General, after 
being satisfied that the parties engaged in the business are obtaining 
money by false and fraudulent promises and representations. 

It will be seen that absolute unity of purpose and principle runs 
through Dr. Wiley's whole record, there is no' wavering or hedging at 
any point. He has not only had the confidence of the people, but also 
of his colleagues engaged in scientific work. He was elected Presi- 
dent of Section C of the American Association for the Advancement 
of Science in 1886; was Secretary of the Council of the American 
Association for the Advancement of Science in 1889, and General 
Secretary in 1891. He became President of the American Chemical 
Society during 1893-4, and was President of the Indiana Academy 
of Science in 1902. He was selected as the delegate from the United 
States to the second, third, fourth and fifth meetings of the Inter- 
national Congress of Applied Chemistry. He was a member of 
the Jury of Awards at the Universal Exposition at Paris, 1900. He 
also has been Professor in Agricultural Chemistry, Graduate School, 
Columbian University, since 1899. He received a medal of the 
first class of the Physicochemical Academy of Italy in 1908. He was 
made Chevalier Merite Agricole in 1900 and Chevalier Legion 
d'Honneur in 1909, He was the Honorary President of the Inter- 
national Congress for the Repression of Adulteration in Geneva in 
1908. In May of last year he was elected the President of the 
U. S. Pharmacopoeial Convention. He is the author of a number 
of books and has published some 60 government bulletins and 
225 scientific papers. 

This series of facts relating to the career of Dr. Wiley shows 
that he is a man who gets results. He is strong in physique and 
is a prodigious worker. That he knows how to get things done 
is not only manifest in the enactment of the Federal Pure Food and 
Drug Law, but in the enforcement thereof. The annual reports of 
the Bureau of Chemistry are simply staggering. In addition to the 
extensive investigations on important food and drug products car- 



386 



Harvey Washington Wiley. 



( Am. .lour. Pharui, 
\ August, 



ried on by the department in Washington during the year 19 lo, and 
also in examination of about 20,000 samples, the following tabulated 
statement of the activities of the twenty-one branch laboratories is 
of interest as indicating in a general way the extent of the work 
done : 



Laboratory 


Imported samples 


Hearings con- 
ducted 


Interstate 
samples 


Miscel- 


Total samples 
analyzed 


Legal 


Illegal 


Floor- 
inspec- 

samples 


Legal 


Illegal 


laneous 
sa-nples 




Boston 


460 


2Q c; 


12 AOA 


674 


7/14. 


2 70 


140 


1,909 




76 


29 


33 


159 


146 


231 


A T 


523 






125 


2,572 


365 


658 


686 


42 


1,684 


Cincinnati 




4 


28 


239 


1,157 


228 


I 


1,409 




1 1 




1 1 


160 


395 


175 


44 


625 


Detroit 


52 


4 


92 


359 


15^ 


144 


31 


382 




59 


22 


365 


116 


192 


144 


44 


461 


Honolulu 1 


272 


144 


677 


131 






8 


424 


Kansas City 


. . . 






103 


125 


127 




252 


Nashville 








157 


191 


65 




256 


New Orleans 


95 


'84 


2,891 


197 


148 


108 


■76 


511 


New York 


2,382 


1,632 


47,821 


1,779 


124 


297 


504 


4,939 


Omaha 






3 


69 


239 


1 10 


100 


449 


Philadelphia 


569 


183 


5.250 


293 


41 


114 


48 


955 


Pittsburg 


47 


54 


227 


197 


162 


216 


55 


534 


Portland 


248 


106 


4,636 


137 


112 


143 


46 


655 


St. Louis 


14 


6 


239 


295 


365 


281 


99 


765 


St. Paul 


74 


13 


233 


85 


136 


55 


4 


282 


San Francisco 


237 


209 


8, 100 


491 


469 


375 


153 


1,443 


Savannah 


65 


40 


26 


159 


105 


51 


19 


280 


Seattle 


277 


137 


1.657 


. 113 


50 


41 


168 


673 


Total 


5.130 


3.087 


58,726 


6,278 


5.710 


3.861 


1,623 


19,41 1 



1 Owing to death of its chief, this laboratory was closed during the month of June ; report 
is total for eleven months. 



Dr. Wiley is not only a man of great executive ability but 
possesses a marvellous amount of patience. The Food and Drugs 
Act of June 30, 1906, became effective on the first day of January, 
1907, and yet in his annual report to the Secretar}/ of Agriculture 
on November 13, 1907, Dr. Wiley says: 

" Previous to this date (January i, 1907) it was necessary to carry out 
the provision of the law providing for the establishment of regulations. 
To this end a committee, consisting of H. W. Wiley, Chief of the Bureau 
of Chemistry, S. N. D. North, Director of the Bureau of the Census, De- 
partment of Commerce and Labor, and James L. Gerry, Chief of the Division 
of Customs, Treasury Department, acting for the Secretaries of Agriculture, 



Am. Jour. Pharm, \ 
August, 1911. j 



Harvey Washing^ton Wiley. 



387 



of Commerce and Labor, and of the Treasury, respectively, prepared a set 
of tentative regulations. Great care was exercised in the preparation of 
these regulations, not only that the provisions of the law should be fully 
executed, hut also that there should be no unnecessary annoyance or burden 
placed upon the trade. It was deemed advisable before the promulgation 
of these regulations to hold public hearings in order to obtain the opinions 
of manufacturers and dealers. To this end, hearings were held in New York 
during the month of September, 1906, and were continued for a week. Upon 
the adjournment of these hearings the committee met frequently for the 
purpose of formulating the regulations, which were finally completed, signed, 
and promulgated on October 17, 1906, as Circular 21 of the Secretary's 
Office. As soon as these regulations were published a great flood of corre- 
spondence poured into the Bureau of Chemistry, necessitating a large increase 
in the clerical force. At the same time, also, arrangement was made for 
increasing the chemical force, to be ready for the increased activities of the 
work incident to the enforcement of the law on the first of January, 1907. 

" Between January i and June 30, 1907, the personnel of the Bureau of 
Chemistry was more than doubled, the increase being divided between the 
clerical force, chemical assistants, and the corps of inspectors. The work 
incident to the enforcement of the law proved to be of far greater magnitude 
than had been anticipated, and up to July i, 1907, no actual prosecutions 
under the interstate feature of the law had been instituted. During this time, 
however, a much more rigorous execution of the law relating to imported 
foods was established. This was possible because under the previous laws 
the machinery for the inspection and analysis of the imported foods had 
been already well organized. The only change which was made, therefore, 
in this service was to transfer the execution of the law from the clause in 
the appropriation bill provided therefor and place it directly under the Food 
and Drugs Act of June 30, 1906. 

" It will not be out of place, however, to mention in this connection that, 
although up to the ist of July no actual cases had been instituted in the 
courts under the Food and Drugs Act, the moral effect of the act was 
apparent in every branch of trade connected with the food industry. One 
of the most gratifying features of this preliminary activity has been the 
almost unanimous support accorded by the trade to the principles of the 
act. In the majority of cases manufacturers of food products, as well as 
dealers therein, have expressed their cordial support of the act and offered 
their hearty collaboration in securing its enforcement. The importance of 
this fact can not be overestimated, since the difficulties of enforcing an act, 
if the entire food trade ivere opposed to it, zvould be practically insuperable."'^ 

I think it was the poet Whittier who said : " Young man, if you 
would be truly successful ally yourself with an unpopular but 
righteous cause." This was what Dr. Wiley did many years ago 
in the cause of pure foods and drugs, and in the prime of his hfe 
the dream of his youth lias become a law. But he was not to stop 

Italics by Editor. 



388 American Pharmaceutical Association. m?""' 

here, for he was charged with the difficult task of seeing that this law 
was judiciously administered. After five years it may be safely said 
that the fruits of his labors are enjoyed, not only by the general 
public, but have redounded to the advantage of the 98 per cent, of 
ethical business men in the United States as well as abroad. 

Henry Kraemer. 



AMERICAN PHARMACEUTICAL ASSOCIATION. 

Philadelphia Branch. 

A special meeting of the Philadelphia Branch of the A. Ph. A. 
was held at the Philadelphia College of Pharmacy, in connection with 
the officers or representatives of a number of other associations 
and the colleges of pharmacy in Philadelphia, to take some action 
which would counteract the recommendation of the Committee on 
Personnel of the U. S. Department of Agriculture that Dr. Wiley 
"be permitted to resign" (see page 381). The President of the 
local branch, Dr. I. V. Stanley Stanislaus, presided, and asked Pro- 
fessor Kraemer to read the resolutions which he had prepared to be 
endorsed, if the members present so desired, and sent to President 
Taft. The following are the resolutions, which were read and 
unanimously adopted: 

Philadelphia, Pa., July 17, 191 1. 

To the Honorable William H. Taft, 

President of the United States. 

The following preamble and resolutions, passed at a special meeting of 
representatives of the organizations named, are respectfully submitted for 
your consideration : 

Whereas, We, the officers and representatives of the Pennsylvania 
Pharmaceutical Association, Philadelphia Association of Retail Druggists, 
Philadelphia Branch of the American Pharmaceutical Association and its 
Scientific Section, Philadelphia Branch of the American Chemical Society, 
The Philadelphia College of Pharmacy, Department of Pharmacy of the 
Medico-Chirurgical College and Department of Pharmacy of Temple Uni- 
versity, in special meeting assembled, having learned that the Committee on 
Personnel of the United States Department of Agriculture has recommended 
that Dr. Harvey W. Wiley, Chief of the Bureau of Chemistry of that depart- 
ment, " be permitted to resign " ; and 

Whereas, The services rendered by Dr. Wiley, as chief chemist have 
been eminent and have revealed a progressive and liberal spirit, and have 



Am. Jour. Pharm.) 

^August, 1911. j 



Book Reviews. 



389 



furthermore been of great benefit not only to the agricultural interests of the 
country but to the American people as a whole; and 

Whereas, Dr. Wiley was the chief promoter of the Federal Pure Food and 
Drugs Law, one of the most beneficent measures ever enacted by Congress, 
and has been untiring and fearless in carrying out its provisions since its 
adoption; and 

Whereas, The drug trade generally throughout the United States has 
always had confidence in the integrity and ability of Dr. Wiley, and have 
endeavored in every manner to support his efforts in the wise and judicious 
administration of the Pure Food and Drugs Law ; therefore, be it 

Resolved, That we heartily endorse and commend the work which Dr. 
Wiley has done in securing the enactment of the Pure Food and Drugs Law, 
and in making the law effective since its adoption, which action has had a 
most wholesome influence upon the practice of pharmacy, both retail and 
wholesale ; and furthermore, be it 

Resolved, That we earnestly deplore any movement which would either 
cause Dr. Wiley to resign at this time, which it seems to us would be little 
short of a public calamity, or tend to hamper him in his efforts to make this 
law effective and thus render it a dead letter. 

Brief addresses were made by the following: Mr. Ambrose 
Hunsberger, Prof. C. B. Lowe, Mr. Christopher Koch, Mr. C. 
Mahlon Kline, Mr. Joseph W. England, Dr. William D. Robinson, 
Prof. C. E. Vanderkleed, Mr. Wm. A. Carpenter, Prof. H. B. 
Morse, Prof. John R. Minehart, Mr. Wm. E. Lee, Mr. Wm. L. 
Cliffe, Mr. Charles Rehfuss, Mr. William Mclntyre and Mr. Wm. 
Martindale. 



BOOK REVIEWS. 

Essentials of Volumetric Analysis. An introduction to the sub- 
ject, adapted to the needs of students of pharmaceutical chemis- 
try. By Henry W. Schimpf, Ph.G., M.D., Professor of Analyt- 
ical Chemistry in the Brooklyn College of Pharmacy. Large 
i2mo. xiv -(- 358 pages, 61 figures. New York: John Wiley & 
Sons. Cloth, $1.50. 

This is the second edition of this book. It has been largely re- 
written and makes a good impression partly for the reason that 
emphasis is placed upon an understanding of the principles under- 
lying volumetric analysis. The author has not adopted the easy 
method of clipping processes from the U. S. Pharmacopoeia, but has 



390 



Book Reviews. 



i Am. Jour. Pharm. 
I August, 1911. 



conscientiously digested the subject, and presented the results in a 
very creditable manner. The volumetric methods are arranged 
in a systematic manner and comprise alkalimetry, acidimetry, precipi- 
tation, analysis involving the use of silver nitrate, sodium chloride 
and potassium sulphocyanate. The oxidation methods involve the 
use of potassium permanganate, potassium dichromate and iodine. 
The reduction methods involve the use of sodium thiosulphate, arse- 
nous acid and stannous chloride. There are also given concise 
descriptions of methods for assaying alkaloidal drugs, phenol, oils, 
sugars, formaldehyde, and alcoholic liquids, together with a few 
simple gasometric analyses, such as a pharmacist may find useful. 
The book ought to be in the hands of pharmacists generally, and we 
believe that even students in chemistry would find the book of 
considerable value. 

History of the Vegetable Drugs of the Pharmacopceia of the 
United States. By John Uri Lloyd, Pharm. M. This is 
Bulletin No. i8 of the Lloyd Library of botany, pharmacy and 
materia medica, published by J. U. and C. G. Lloyd, Cincinnati, 
Ohio. 

The volume at hand brings to mind the quarterly publication 
entitled " Drugs and Medicines of North America," which was 
published by the Lloyd Brothers in 1884. This was an ambitious 
undertaking, and to pharmacists it was much like Gray's Flora of 
North America to botanists. Probably no two men were by nature 
and inclination as well as literary ability so well qualified to give 
a record of American medicinal plants including the history, botany, 
chemical constituents and pharmaceutical preparations as these 
authors. This work was suspended when No. 5 of Volume II was 
published in 1887. A few years later it was proposed largely 
as a result of the interest taken by Professor Fliickiger in the subject, 
that a " Pharmacography of North American Medicinal Plants and 
Drugs " should be written conjointly by himself and Professor 
Lloyd. The death of Fliickiger, however, terminated the enter- 
prise, bringing to Professor Lloyd, as we can well understand, " one 
of the greatest disappointments of his fife." 

In the present volume the history of the vegetable drugs of the 
U.S. P. Eighth Revision are given. " Only enough is chronicled of 
each drug's beginning to point to the peoples or individuals who 
introduced it to medicine and pharmacy, no attempt being made to 



Am. Jour. Pharm,") 
[August, 1911. ]■ 



Book Reviews. 



391 



follow the details of subsequent manipulations." A bibliography 
with over 700 references to books, monographs and articles com- 
pletes this Bulletin. There are also included portraits of Dr. Rice 
and Professor Remington, the former being elected chairman of 
the Committee of Revision in 1900 and the latter Dr. Rice's 
successor. 

This Bulletin contains very much valuable information and will 
not only be found useful as a reference book by the student but 
makes interesting reading. A rather curious omission is noted in 
the bibliography. While certain American medical journals are 
cited, the American Journal of Pharmacy is not mentioned, 
although some references to Bastin's articles (as on p. 91) are given 
in the text and other references are made to this Journal throughout 
the Bulletin. The same thing may be said of other publications, 
although fortunately the references are given in the text in connec- 
tion with the discussion of the individual drugs. So that as a 
matter of fact the bibliography is much more extensive than would 
appear from the figures given. 

Handbuch der Pharm akognosie von A. Tschirch. Lief. 22-25. 
Leipzig : Chr. Herm. Tauchnitz. Each Lieferung 2 marks. 

In these brochures we have a continuation of the class of subjects 
introduced in the preceding Lieferungen and include the following: 
starch-yielding substances; inuHn containing drugs; drugs contain- 
ing triticin; polysaccharides occurring in membranes of plants as 
cellulose, lichenin substances, pectinous substances, mucilages and 
gums. The same high character of work is maintained and it is 
truly remarkable that it has been possible for Professor Tschirch to 
write so many original papers and publish at the same time this 
epoch-making book. It should be in the library of every pharma- 
ceutical and medical school as well as in manufacturing laboratories. 
Of course pharmacognosists and food analysts are securing the 
Lieferungen as they are published, but owing to the general interest 
in many of the subjects treated, particularly by reason of the excel- 
lent illustrations, the latter half of the work might well be placed 
in technical schools, universities, and museums where raw materials 
are exhibited and studied, as well as employed for demonstration 
in connection with lecture courses. Botanists will find this work 
of Tschirch's like that of Wiesner's Die Rohstofife," and Czapek's 
" Biochemie der Pflanzen " of much value as a reference book. 



392 



Book Reviews. 



( Am. Jour. Pharm. 
t August, 1911. 



Pharmakognostische Rundschau iiber das Jahr 1910. Bericht 
iiber die im Jahre 1910, periodisch crschienenc Literatur aus deni 
gebiete der Drogenkiinde und ihrer Hilfswissenschaften, von 
Prof. Dr. W. Mitlacher, Dr. O. Tunmann and Dr. M. Winckel. 
191 1. Verlag der Pharmazeutischen Post, Dr. Hans Heger, 
Wien, I, Pestallozzigasse 6. $2.00. 

It is rather stimulating to pharmacognosists to find that a volume 
of nearly 300 pages, containing a digest of the important pharma- 
cognostical literature for 1910 is available in this form. In addi- 
tion to some 50 pages in which are considered some general articles 
of a historical and special nature, abstracts of the various drugs 
are given under the respective plant families, and the latter are 
arranged in alphabetical order. The general disposition of the 
matter is such that it forms a very handy reference work. The 
abstracts are quite full and, having been prepared by specialists, con- 
tain all of the essential features. It is hoped that the sales of this 
work will be sufficiently great to warrant a continuation of its pub- 
lication. When we consider the importance of the subject and the 
excellence of the work done, it would seem unnecessary to say that 
it is indispensable and should be in the libraries of our colleges and 
schools of pharmacy, and of botanists, pharmacognosists and food 
analysts. 

Revue des Medicaments Nouveaux et de quelque medications 
nouvelles. Par C. Crinon. i8e Edition. Paris : Vigot Freres, 
Editeurs, 23, Place de I'Ecole-de-Medicine. 191 1. 

Among the new substances considered in the eighteenth edition 
of this work the following may be mentioned : Trichloracetylsalicylic 
acid, acoine, antodyne, asurol, bromhydrate of codeine, digistro- 
phane, eulatine, hexamethylenetetramine-guiacol, pantopon, seiffenol, 
606, tasi, thilavene and zincopyrine. 

Lectures on Cosmetic Treatment. A manual for practitioners. 
By Dr. Edmund Saalfeld. Translated by I. F. Halls Dally, 
M.D., with an introduction and notes by P. S. Abraham, M.D. 
Paul B. Hoeber, 69 East 59th St., New York. 

This work has been written apparently with the view that cos- 
metic treatment is for the regular practitioner and not for the 
so-called beauty specialist." Professor Josef has well said : The 



Am. Jour. Pharm, » 

August, 1911. S 



Book Reviews. 



393 



subject of cosmetics has been too long neglected by the medical 
profession, and on this account has, unfortunately, passed into the 
hands of unc[ualified persons." It is probably true that a great 
many patients who could and should be treated by the general prac- 
titioner, if he only knew how, drift away from him and waste their 
time and money on various advertised nostrums or on other quack- 
ery. Dr. Saalfeld's book is written on strictly professional lines, 
and the work will no doubt prove useful to the general practitioner as 
well as to the dermatologist. 

Some Common Remedies and Their Use in Practice. By Dr. 
Eustace Smith. Paul B. Hoeber, 69 East 59th St., New York. 

Among the subjects treated in this volume are the following: 
On an Unjustly Neglected Remedy — Tartarated Antimony (tartar 
emetic) ; On the Internal Use of the Oil of Turpentine; On the Use 
and Misuse of Iron Remedies ; On the Use of Alkalies in Practical 
Medicine ; On Antispasmodics and the Cure of Spasm ; On Some 
Uses of Opium ; On the Use of Sodium Salicylate in Certain Serous 
Inflammations. The chapters making up this book are reprints of 
articles contributed to The British Medical Journal at intervals dur- 
ing the years 1908 and 1909. Their greatest interest lies in the 
fact that the author records his experience in using some of the 
standard medicines. Nearly every practitioner of experience could 
write a book of a similar character, and the young practitioner 
is the one who would be most benefited by a perusal of this work. 

Compte Rendu du Xme Congres International de Pharmacie. 
Tenu a Brusselles du ler an 6 Septembre 19 10. Par Dr. A. 
Schamelhout. Brusselles : Imprimerie-Lithographie L. Vogels, 
Rue Verte, 48-50. 19 11. 

This volume contains an official account of the proceedings of the 
Tenth International Congress of Pharmacy held at Brussels during 
the first week of September last year. The papers which were 
read and the communications which were presented are printed in 
full. The discussions in connection with the various papers and 
reports are given in abstract and show careful editing upon the 
part of Dr. Schamelhout, the secretary-general of the Congress. 
An interesting account is given of the various excursions, fetes and 
receptions that were held. In addition to the list of names of mem- 
bers of the Congress we find a number of photographs of those 



394 



Wallace Procter. 



/Am. Jour. Pharm. 
\ August, 1911. 



prominent in the work of the Congress, as of the two Presidents, 
Dr. Albert Derneville and Dr. Olivier Kusnick; the Secretary- 
general, Dr. Albert Schamelhout ; and the members of the Committee 
on Organization. 

While the reports that have been published, particularly in the 
foreign journals (see also this Journal, 191 i, p. 24), show that the 
work of the Tenth International Congress of Pharmacy was emi- 
nently successful, it is still more apparent from the Proceedings at 
hand that a broad fraternal and international spirit dominated the 
entire meeting, and we feel sure that much good must redound to 
professional pharmacists throughout the world. The pharmacists of 
our country are encountering the same difficulties and are attempting 
to solve the same problems as those of other countries. In each 
country some progress is being made and it is quite possible for the 
pharmacists of one country to proht by the experiences of those 
in other lands, and thus eventually the best practice will be the 
universal practice. It is certain that we in the United States can 
profit much by the careful perusal of the deliberations of this 
Congress and, if we endeavor to catch the stimulating influence of 
the master minds who contributed to this session at Brussels, our 
professional and commercial work must be of a higher and more 
efficient character. 



WALLACE PROCTER, Ph.M. (1851-1911). 

Wallace Procter, Ph.M., was born April i, 1851, in Philadelphia, 
at the southwest corner of Ninth and Lombard Streets. He was the 
only son of William Procter, Jr., and Margaretta, his wife, whose 
maiden name was Bullock. (She was the first cousin of Charles 
Bullock, for many years the President of the Philadelphia College of 
Pharmacy.) Prof. William Procter had a daughter, Mary Gold- 
smith Procter, who married Samuel S. Green, and is now living at 
Barto, Florida. 

Wallace was sent to private schools by his father for his early 
education. He then went to the Friends' Central School and gradu- 
ated at the head of his class. He entered his father's store in 1868, 
and the next year matriculated at the College of Pharmacy. He 
successfully passed the examinations in the Junior course, and the 
following year he did not re-enter college, but acquired a practical 
knowledge of the drug business in the store. In October, 1871, he 



Am. Jour. Pharm. \ 
August, 1911. j 



Wallace Procter. 



395 



entered the Senior course and graduated in 1872, winning the Alumni 
Gold Medal. Magnolia Tripetala " was the subject of his thesis. 

After graduation he assisted his father in the drug business, and 
on the death of his father on February 10, 1874, he entered into 
copartnership with David Preston, Ph.G. (1865), the firm's name 
being Wm. Procter, Jr., Co. This partnership continued till Oc- 
tober, 1890, when Wallace Procter purchased from Lancaster 
Thomas the drug business at 1900 Pine Street. Here he remained 
in active practice for twelve years. On December 17, 1906, he 
entered the service of the Ohio Valley Drug Company, at Wheeling, 
West Virginia. He was given full charge of the laboratory and 
manufacturing department and he remained in this position until 
the day of his death, which occurred on May 27, 191 1. 

Wallace Procter was a devoted and earnest worker for his Alma 
Mater. He was elected a member of the Board of Trustees in 
1883 ; and in 1888 he became a member of the Committee on Ex- 
aminations, and its Chairman in 1890. His keen mind and compre- 
hensive knowledge of pharmacy especially adapted him for this 
position. The questions which he propounded were always prac- 
tical and thoroughly adapted to ascertaining the accuracy and 
extent of the knowledge of the student. He was no mere copier of 
old or revamped questions. He had but one thought in his mind, 
to develop the thinking qualities and reasoning powers of the student, 
and he attached very little value to mere memorizing. He served 
seventeen years in this capacity. 

He was elected a member of the Committee on Instruction, and 
also of the Committee on Property; and in 1894 he became a 
member of the Publication Committee of the American Journal 
OF Pharmacy. In 1893 he was appointed a member of the Commit- 
tee on Pharmaceutical Meetings of the College. 

He was an active member of the Alumni Association ; served 
as its Recording Secretary from 1 876-1 878, and wsis a member of 
the Executive Board for nine years. He was twice elected First 
Vice-President, 1878 and 1885, and became President of the Alumni 
Association in 1886. In 1887 he was re-elected member of the 
Executive Board, and continued in this capacity a number of years. 
Wallace Procter was one of the pioneer workers in this association, 
in the early days wlien this meant devoted and continued service 
under discouraging circumstances. He lived to see the association 
flourish and grow, and he was foremost in encouraging college 
spirit, 



396 



Wallace Procter. 



( Am. Jour. Pharm. 
\ August, 1911. 



He became a member of the American Pharmaceutical Associa- 
tion in 1874, and a member of the Pennsylvania Pharmaceutical 
Association in 1881. He contributed many papers to the various 
pharmaceutical organizations and journals. Like his father he 
accepted service in many capacities where the sole reward was the 
simple satisfaction of doing good and advancing the interests of 
pharmacy. 

Wallace Procter married Susan Ridgeway Shreve, of Mount 
Holly, New Jersey. It will be remembered that Mount Holly was 
the summer home of Prof. William Procter, and Wallace greatly 
enjoyed the freedom of a life in the open air, amid congenial sur- 
roundings of fruit trees, grape vines, and the sights and sounds of 
rural life. It was here that he met the maiden who was to become 
his wife, and who still survives him. 

Three daughters remain to cheer their mother — Edith Harrison, 
Marian Grigg, and Margaretta Lippincott. 

This simple record of the life work of Wallace Procter gives 
but a faint idea of his achievements. He possessed an excellent 
mind, developed by education and environment. In the latter years 
of his life he gave much time to books. He was an omnivorous 
reader, and all branches of pharmacy claimed his attention. 

His admiration for his father and the great mission which the 
latter fulfilled were ever before him ; and, while he did not inherit 
the love for original investigation which dominated Prof. Procter's 
personality, Wallace had an analytical mind and never trusted to 
surface indications. The son practised what the father taught, and 
added knowledge fitted for his time and generation. 

When he transferred his activities from Philadelphia to Wheel- 
ing, his quiet unobtrusive manner and his genial qualities soon 
endeared him to a host of friends. Further acquaintance added to 
his popularity, and the Ohio Valley Drug Company sent Wallace 
Procter to the State association meetings as their representative, and 
he became one of the most valued members of the Virginia Pharma- 
ceutical Association. 

On May 9, 191 1, he sufifered a stroke of paralysis. His physi- 
cians, realizing that his condition was serious, recommended a 
return to his native city ; and upon the arrival of his wife, the 
sad journey from the hospital, at Wheeling, to Philadelphia was 
accomplished ; and though under distressing circumstances, it was 
cheered by the reflection that his friends turned out en masse at 
the home and in the railroad station, and did everything in their 



"^^Au^uimL^"} Philadelphia College of Pharmacy. 397 

power to testify to the devoted wife the honor and the affection which 
Virginians always exhibit to those whom they love and trust. 

Wallace Procter died on May 27, 191 1, and the Board of Trus- 
tees, and his college friends in Philadelphia, were present at the 
last sad rites. He was laid to rest beside his father in Mount 
Holly, the beautiful place which had witnessed more days of real 
happiness to both than any other spot on earth. 

J. P. R. 



THE PHILADELPHIA COLLEGE OF PHARMACY. 

QUARTERLY MEETING. 

The quarterly meeting of the members of the College was held 
June 26th at 4 p. m., in the Library. The President, Howard B. 
French, presiding. Fifteen members were present. The minutes of 
the Annual Meeting held March 27th were read and approved. The 
minutes of the Board of Trustees for the meetings held March 7th, 
April 4th and nth, May 2d and i6th, were read by the Registrar, 
and approved. The Report of the Committee on Membership was 
read by Prof. C. B. Lowe, Chairman. Some statistical information 
is given in the report and mention made of a number of members 
who are in arrears for non-payment of annual dues. The members 
are urged to interest those deemed worthy of membership to have 
them unite with the College. 

The Report of the Committee on Necrology was read by Prof. 
Henry Kraemer. Since the last report three members have died. 
Caleb R. Keeney died February ist, 191 1 — a graduate of the class 
of 1846. He joined the College in 1852. He was the oldest gradu- 
ate and at the same time one of the oldest members. 

Thomas M. Newbold, died April 2d, 191 1. Joined the College 
in 1871. 

Wallace Procter, died May 27th, 191 1. Joined the College in 
1874. He was the son of the late Professor William Procter. 

The College has lost through the death one of our Honorary 
Members, Professor Attfield (see this Journal, p. 358). 

Another name worthy of mention, although not a member of the 
College, was one of its most distinguished graduates. Professor 
Carl S. N. Hallberg. 

The Plistorical Committee, through its Chairman, George M. 
Beringer, reported that they had not been unmindful of their duties, 



398 Philadelphia College of Pharmacy. f ^'°(,4°";t; im™' 

but as most of the members of the Committee were also members 
of the College Committee on the revision of the United States Phar- 
macopoeia that much of their time of late has been occupied with that 
work. 

The Committee on By-Laws, to' whom was referred the sug- 
gestion to change the time of holding the Pharmaceutical Meetings, 
reported an amendment to Article XI, Section i. Action upon which 
lies over till the next meeting of the College. 

The Report of Delegates to the 34th Annual Meeting of the 
Pennsylvania Pharmaceutical Association held at Bedford Springs, 
June 20th to 23d, was presented by Professor Lowe. Among the 
valuable reports were those on " Adulterations " and " Trade Inter- 
ests," both of which were quite full and of great interest. The 
report of the Committee on Legislation, by its Chairman, John C. 
Wallace, aroused much interest. The Pharmacy Bill as amended 
was referred back to the Committee on Legislation with instruc- 
tions to prepare a bill and submit to the members one month 
prior to the next Annual Meeting. Some 30 papers were pre- 
sented by the Committee on Papers and Queries. The prize of 
$20 for the best paper read at the previous meeting was awarded to 
Mrs. C. H. La Wall. 

Mr. J. L. Lemberger was elected President. Of the nine ap- 
pointed delegates, six were present. So many of the graduates of 
the College were in attendance that the meeting almost looked like 
an Alumni reunion. 

The next meeting of the Association will be held at Buena 
Vista. 

The report of Delegates to the New Jersey Pharmaceutical 
Association was read by Mr. George M. Beringer, Chairman. 

The Annual Meeting was held at Asbury Park, N. J., June 
13-16. There was an address of welcome by the Mayor of the 
city. A proper recognition of " Flag Day " was shown by draping 
the presiding officer's desk with Old Glory, and the entire Asso- 
ciation joining in singing the " Star Spangled Banner." Four of 
the delegates from the College attended the Meeting and were cor- 
dially welcomed. The meeting this year was notable for increased 
attendance and interest in the proceedings. The papers were more 
numerous and varied. Professor Kraemer contributed a very in- 
teresting paper on the Pliarmacognosy and History of the Echinacea. 
The other papers presented and discussed were on Standard Sur- 
gical Dressing, by Mr. F. B. Kilmer; Review of the German 



^'"AuguJt, i9ii""} Philadelphia College of Pharmacy. 399 

Pharmacopoeia, by George M. Beringer, Ph.M. ; Window Dressing 
by Mr. Holzhauer ; Neutral Suspension of Salvarsan, by Mr. George 
M. Beringer, Jr. ; Official Pepsin Preparations and Official Iron 
Preparations, by P. E. Hommel ; Calx. U. S. P., by Prof. Chas. H. 
La Wall. The greatest interest was manifested in the discussion of 
a proposed new Pharmacy Act for the State. A draft of a proposed 
bill was presented in printed form as a basis for the discussion. The 
Association expressed itself as to the principles tO' be included in a 
new Pharmacy Act to be presented to the next session of the Leg- 
islature. This included a "prerequisite " clause as a leading 
feature. On the whole the meeting this year was considered a very 
successful one and fraught with possibilities for many pharmaceutical 
advances. 

The President made the following appointments : 

Delegates to the American Pharmaceutical Association Meeting 
to be held in Boston, August 14-18; Joseph P. Remington, Henry 
Kraemer, C. B. Lowe, A. W. Miller, George M. Beringer. 

Historical Committee: George M. Beringer, Jacob M. Baer, 
Henry Kraemer, Warren H. Poley, C. A. Weidemann. 

Committee on Necrology : Henry Kraemer, E. M. Boring, C. A. 
Weidemann. 

Committee on Nominations : William L. Cliffe, Charles H. 
La Wall, James C. Perry, Theodore Campbell, George B. Weidemann. 

Professor Kraemer proposed the names of two gentlemen for 
Honorary Membership. According to the rules action is deferred 
till the next meeting of the College. 

Professor Kraemer referred to the death of Wallace Procter, 
who was for many years a member of the College and of the Board 
of Trustees, and moved that a committee of three be appointed to 
draft suitable resolutions to his memory, which being agreed to, 
the President appointed as members of the Committee : Joseph P. 
Remington, Joseph W\ England and C. A. Weidemann. 



ABSTRACTS EROM MINUTES OJ^^ THE BOARD OE TRUS- 
TEES. 

March yth. Sixteen members present. Committee on Library 
reported 1350 accessions (old and new books) from October 26th 
to Eebruary ist. Many of the cases had been cleaned. 132 persons 
had used the Library during the month. Committee on Examina- 



400 Philadelphia College of Pharmacy. {^\ngnk Ini"^' 

tions reported that Edward C. Denzler had successfully passed the 
examination for the Certificate of Proficiency in Chemistry, and 
was awarded the Certificate. 

Committee on Announcement asked that they be authorized to 
issue a hand-book of condensed information for the use of pros- 
pective students. Such a book had been prepared and the Committee 
was given the power to issue two thousand copies. 

The merger of the " Alumni Report " with the " Bulletin " had 
been very favorably received, and it was believed the change would 
prove a beneficial one. 

April 4th. Fourteen members were present. J. L. Lemberger 
presiding. A communication from the Secretary of the College was 
read reporting the names of the officers of the College and three 
members of the Board elected at the Annual Meeting of the College, 
held March 27th, 191 1. Upon organization of the Board, Mr. 
George M. Beringer was re-elected Chairman, and Walter A. Rum- 
sey, Vice-Chairman, for the ensuing year. Jacob S. Beetem was re- 
elected Registrar. The standing committee for the ensuing year 
were announced by the Chairman. Committee on Library reported 
286 accessions ; 325 persons had used the Library during the 
month. 

April nth. Sixteen members present. Committee on Instruc- 
tion presented a lengthy report covering the work of all the depart- 
ments of the College in detail and making a number of recommenda- 
tioins, which were acted upon separately and adopted with slight 
alterations in several of them. The Committee on Appropriations 
reported the various estimated amounts to be allowed the Com- 
mittees and Departments authorized to make expenditures. 

May 2d. Sixteen members present. Committee on Library re- 
ported 313 books stamped, classified and shelf-listed, and that 192 
persons had used the Library during the month. 

Committee on Examinations reported Charles Duvoisin as having 
passed the examination for Certificate of Proficiency in Chemistry 
and therefore entitled to the certificate, which was awarded him. 

May i^^th. George M. Beringer, Jr., was elected to active mem- 
bership. Seventeen members present. Committee on Examinations 
reported the names entitled to the degree of Doctor in Phar- 
macy, Pharmaceutical Chemist, and Certificate of Proficiency in 
Chemistry and Pure Food and Drug Course, and recommended 
their election. A ballot being taken they were declared elected. 



Am. Jour. Pharm.) 
August, 1911. J 



Correspondence. 



401 



The award of prizes to those entitled to them was announced, as 
also the various speakers who were to present the prizes to the 
recipients on the night of the Commencement. 

Commattee on Commencement reported that Prof. Willis L. 
Moore, Chief of the Weather Bureau, had kindly consented to 
deliver the annual address. C. A. Weidemann, M.D., 

Recording Secretary. 



CORRESPONDENCE. 

BOARD OP TRUSTEES, UNITED STATES PHARMACOPCEIAL CONVENTION. 

The General Medical Convention edited and published the first 
Pharmacopoeia in the series of what is now known as the Pharmaco- 
poeia of the United States of America. It was published in Boston, 
December 15, 1820. The convention provided for the revision of 
the Pharmacopoeia in 1830, the convention being then known as the 
National Medical Convention. The same name was applied to the 
conventions of 1840 and 1850. In i860 the name was changed to 
the National Convention for Revision of the Pharmacopoeia. In 
1900 the name was again changed tO' the United States Pharmaco- 
poeial Convention, which was duly incorporated. Prior to 1900 
business matters, as well as the work of editing, were taken care of 
by the Committee of Revision. With the incorporation in 1900, 
business affairs were separated from the work of revision and placed 
in the hands of a Board of Trustees, having the management of 
affairs and funds of the convention. The By-laws provide that the 
Board of Trustees shall transact business involving financial or other 
matters that may be for the best interests of the convention, 
and perform such other duties as the convention may from time to 
time direct. The following is the Board of Trustees, as constituted 
by the convention of May, 1910: 

James H. Beal (Chairman), Henry M. Whelpley (Secretary), 
Frederick W. Meissner, Jr., William Jay Schieffelin and George H. 
Simmons. Joseph P. Remington and Harvey W. Wiley are ex- 
officio members. The officers were re-elected for the ensuing year. 

The Board held its first annual meeting for the decennial period, 
1910-20, at Philadelphia, May 5 and 6. All members were present. 

The Board appropriated funds for use in paying necessary 
expenses in the work of revision incurred by members of Executive 
Committee under the direction of Chairman Remington. 



402 



Correspondence. 



{Am. Jour. Pharm. 
AugUHt, 1911. 



The Board decided to withdraw from sale those copies of the 
U.S. P. VlII in which additions and corrections have not been 
incorporated in the text. 

An inventory has been prepared of all of the articles of per- 
manent value purchased since 1900. A record is being made of the 
location and condition of these articles. 

Insurance has been taken out on the electroplates for both the 
Spanish and English editions which are in the hands of the publisher. 
Also, on the copies of both the English and Spanish editions which 
are on sale in the hands of agents. 

An auditing committee examined the accounts of the Treasurer, 
Samuel L. Hilton, and Secretary of the Board, H. M. Whelpley, 
and found the same correct. Expenditures are first authorized by 
the Board and the bills approved by the person under whose super- 
vision the expense is incurred. All bills are next sent to the Secre- 
tary of the Board to be audited. The Secretary then issues a 
voucher check which he signs and forwards to Chairman Beal, who 
in turn signs and forwards the voucher check to Treasurer Hilton, 
who signs same and mails it to the payee. The original bills with 
notations are preserved with the records of the Secretary of the 
Board. The Treasurer of the Convention and the Secretary of the 
Board keep duplicate accounts of receipts and expenditures, as shown 
by the voucher checks. The following is a summary of the same for 
the fiscal year just closed (May i, 1910, to April 30, 191 1) : 



Rfxeipts. 

May 23, 19JO, To balance from Treasurer 1900-1910. . . . $8394.01 

May 23 to April 30, 191 1, Sales English Edition 6188.02 

May 23 to April 30, 191 1, Sales Spanish Edition 1169.35 

May 23 to April 30, 191 1, Receipts from Use of Text. . . . 290.00 

July I, 1910, Interest on Deposits, American S. & T. Co.. 88.91 
January 3, 1911. Interest on Deposits, American S. & T. 

Co 83.02 

Total Receipts $16,213.31 



Expenditures. 

ipio-ii. Expenses iQio Convention. — Supplies, $79.70; print- 
ing, $53.25; general, $15.73; stenographic report, $375.38; clerical, 
$198; abstract, $345.17; total, $1067.23. 

/. Revision. — Clerical, $1847.50; meetings, $13.89; supplies, 



Am, Jour. Pharm. 1 

August, 1911. j" 



Correspondence. 



403 



$1140.97; postage and telegraph, $146.88; experts, $52.60; general, 
$112.67; total, $3314-51. 

//. Publication and Sales. — English edition, $1952.56; Spanish 
edition, $271.12; general, $9. Total, $2232.68. 

///. Administration. — Meetings, $330.10 ; clerical, $666; supplies, 
$154.65; postage and telegraph, $67.50; general, $41.53. Total, 
$1259.78. Grand total, $7874.20. 

Cash on deposit American Security Co., to balance, as shown 
by Treasurer Hilto^n's books and verified by the bank, $8339.11. 

Henry M. Whelpley, 
Secretary Board of Trustees, U.S.P.C. 



KENTUCKY AGRICULTURAL EXPERIMENT STATION. 

To the Kentucky Retail, Wholesale and Manufacturing Druggists: 
Two years' work under the Kentucky Food and Drugs Act has 
convinced those engaged in the enforcement of the drug sections of 
that Act, that there are two classes of adulteration : first, adultera- 
tions due to wilful intent or gross carelessness ; second, adulterations 
due to various trade and professional problemiS, which this office 
believes can be better overcome through mutual assistance rather 
than prosecution. 

For the purpose of introducing educational and co-operative 
methods with respect to the second class problems, this Division 
proposes to conduct a short term school for druggists and others 
engaged in the drug business, of about ten days' duration, during 
the last of April or the first of May. It is proposed to take up at 
this school the following subjects: {a) The general application of 
the State and Federal pure food laws for the drug business; {b) 
the drug regulations and notices of judgment under the Federal 
law; (c) the regulations under the State law; {d) the proper 
labelling oi patent and proprietary medicines under the law; {e) 
the proper labelling of U.S. P. and National Formulary products 
under the law; (/) necessary equipment for a druggist's laboratory; 
{g) drug store management and equipment; {h) problems con- 
nected with the preparation, storage and handling of various pharma- 
ceutical preparations; {i) standard weights and measures; (/) 
the soda fountain; (k) other similar subjects. 

These matters will l)c presented hy the experts of this office 



404 



Correspondence. 



( Am. Jour. Pliarm. 
\ August, 1911. 



and by pharmacists who will be invited to assist. The Division 
also proposes to invite the manufacturers of some of the pharma- 
ceuticals with which druggists have difficulty, to send their chemists 
or manufacturing managers to give special lectures with respect to 
the proper treatment and handling of such products. 

This office would like to have your views of the school, and 
the plan outlined above, with any further suggestions, as to whether 
or not anyone connected with your firm will attend, and as to the 
best date. 

A blank for reply is enclosed herewith. Please answer at your 
earliest convenience. Respectfully, 

R. M. Allen, 

March 22, 191 1. Head of Division. 



American Journal of Pharmacy, 
Philadelphia, Pa. 
Gentlemen : Enclosed find three resolutions adopted at the 
last meeting of the Pennsylvania Pharmaceutical Association. 

The one regarding the Pure Food and Drugs Act and also the 
one concerning Dr. Wiley are particularly pertinent at the present 
time, in view oi the activity of the food and drug Dopers." 

These resolutions have been sent tO' the President of the United 
States, the Senators from Pennsylvania, and the Congressmen from 
the State of Pennsylvania. 

Thanking you for your uniform courtesy and assistance. 

Very sincerely yours, 

E. F. Heffner, 
July 21, 191 1. Secretary. 

Resolution: We, the members of the Pennsylvania Pharmaceu- 
tical Association, in convention assembled, do hereby 

Resolve, That we place ourselves on record as favoring such 
necessary amendments to the Federal Food and Drugs Act of June 
30, 1906, as will prevent the misbranding of food and drug products 
either as to composition, curative action or in any other particular. 

Resolution: We, the members of the Pennsylvania Pharmaceu- 
tical Association, in convention assembled, do hereby 

Resolve, That we disapprove of and denounce the underhanded 
and unfair methods which have recently been used by the organiza- 
tion called the American Protective Association in attacking Dr. 



^"iugrt. im'"' } Correspondence, 405 

Wiley, who has so fearlessly fought for honest standards in both 
foods and drugs ; for, while many persons may honestly object to 
certain rulings and proceedings brought under the Federal Food and 
Drugs Act, we believe that such objections as are meritorious and 
such opposition as is worthy of support should be brought in an open 
and fearless manner and without subterfuge. 

Resolution: Whereas, there is pending in Congress an act known 
as " The Sherley Bill," H.R. No. 8,887, under the provisions of 
which it is proposed to levy a stamp tax of 2^ per cent, based upon 
the retail price of so-called patent " or proprietary " medicines 
and all toilet preparations of a proprietary character, and 

Whereas, Experience has demonstrated that this burden will 
fall heavily upon the retail druggist because the added cost cannot 
be passed to the consumer as the retail price is fixed by the manu- 
facturer, and 

Whereas, The only medicines that are really patented, viz., the 
various imported and domestic synthetic products will not come 
under the provisions of this act, for reason that they are classified 
as uncompounded medicines upon which this tax would not be levied ; 
therefore be it . 

Resolved, That we, the members of the Pennsylvania Pharmaceu- 
tical Association, in convention assembled, do solemnly protest 
against the enactment of this measure, believing it tO' be a direct tax 
upon a single class of business, and therefore burdensome and unjust. 



PENNSYLVANIA PHARMACEUTICAL EXAMINING 

BOARD. 

Licensed as Pharmacists. 

Announcement was made by the State Pharmaceutical Examin- 
ing Board on July 6th that 334 out of 450 applicants for State licenses 
had been successful, the number qualifying as pharmacists being 199 
and as assistants 135. 

Philadelphians who passed the examinations are : 
Pharmacists: Samuel Baradofsky, William D. Baun, Jennie Bel- 
litz, Louis Bell, Meyer Bloomfield, Frank E. Houston, De Wilton 
S. Berry, Samuel J. Brahin, Osher Briskin, Robert O. Bricker, Lloyd 
Burtt, Franklin C. Brush, Louis E. Christopher, Philip Cohen, D. 
Wayne Darrah, Charles C. Eberly, David W. Eisman, Lewis 
Fleisher, Nathan M. Friedman, Walter J. Gaskill, Samuel Click, 



4o6 



Correspondence. 



{Am. Jour. Pharm. 
August, 1911. 



Jacob Goldberg, Charles S. Gutzeit, Morris Haimowitz, Gerald J. 
Harrigan, Max Heller, Carl F. Kaehler, Nathan Kaufman, John L. 
Kooker, Jr., James Kramer, John F. Kratz, Harry Lashinsky, Re- 
becca Levy, Andrew F. Lippi, Michael J. Lovenstein, Francesco 
Megaro, Samuel Millrood, Louis H. Myers, Mabel Nelson, Lewis 
W. Oswald, A. A. O'Daniel, John M. O'Donnell, Geo. W. Patterson, 
Jr., Benjamin Promisloff, John W. L. Purcell, Albert Rachmil, Julius 
Rapaport, Nathan Rosensweet, Samuel Rosin, Leon Ross, Thomas 

B. Tanner, Isador P. Salinsky, Fred A. Schuenemann, Edward 
Seldes, Nathaniel J. Segal, Stanley A. Shiles, Samuel A. Silk, M.D., 
Israel Spiers, Ethelbert Steelman, Morris Stein, William H. Stern- 
thai, William H. Udell, Lewis Viner, Llewellyn J. Watkins, E. 
Leonard Weiszgerber, Leon M. Wolchek, Harry Woorman, Jos. 
L. Murray. 

Qualified Assistants: Gerson Azoff, Rose Blieden, Maurice 
Brown, Herman J. Broude, Charles A. Buohl, Herbert H. Boyer, 
Ernest Bernabei, F. W. Campbell, Joseph Duffy, James T. Fiedler, 
Harry Friedman, M. S. Glauser, Herman Leo Hinski, Ralph A. 
Hurley, William F. Kalesse, Karl Krogh, Albert F. Keller, Morris 
L Lopoten, Jacob Lubin, Moses Minzes, Myer Matrick, Patrick 
P. Maloy, Fred W. Martin, Leah Nichols, Esther Nicholas, H. E. 
Newton, Blair G. Rumsey, L. E. Rothberg, C. J. Rabin, Clifford 
Raser, Henry L. Reinish, Hyman B. Stern, M.D., Sol. E. Streitfeld, 

C. B. Sterner, J. Harry Swain, Edison Shoemaker, Henry A. Stauf- 
fenberg, Tany Taboror, Anna Teller, B. O. Tegge, John Thomas, 
Antonio Venuto, David Weinberg, Hirsli Wilderman, W. S. Wig- 
nall, Reuben L. Walton, O. W. Wickham, Charles H. Yeagle, and 
Nathan Zonies. 

The colleges of pharmacy and the number of applicants fromi each 
who' graduated in 191 1 and took the examinations for applicants 
desiring registration as pharmacists, were as follows : 

Philadelphia College of Pharmacy, 70, of which 66 passed the 
examination and 4 failed; Medico-Chirurgical College, department 
of pharmacy, 34, of which 28 passed and 6 failed ; University of 
Pittsburg, department of pharmacy, 44, of which 42 passed and 2 
failed; Temple College, department of pharmacy, 15, O'f which 14 
passed and i failed ; Brooklyn College of Pharmacy, i applicant and 
I successful. 

The next examinations given by the board will be conducted in 
the Williamsport High School, Williamsport, Pa., on August 24 
and 25. 



THE AMEEIOA]^ 

JOURNAL OF PHARMACY 



SEPTEMBER, igii 



THE PHARMACOPCEIAL STANDARD FOR DESICCATED 
THYROID GLANDS/ 

By Reid Hunt and Atherton Seidell, 

[Division of Pharmacology, Hygienic Laboratory, U. S. P. H. and M. H. 
Service, Washington, D. C] 

During the past few years a great many experiments have been 
made in this laboratory upon the relation between the physiological 
activity of thyroid and its iodine content. These experiments, and 
practically all others that have been described in the literature, 
defmonstrate this parallelism; it may therefore be concluded that at 
present the most satisfactory way to standardize thyroid is by 
means of the determination of the organically combined iodine which 
it contains. From the standpoint of the Pharmacopoeia the question 
resolves itself simply into the selection of the rnost satisfactory 
method for the iodine estimation and the adoption of the most 
reasonable percentage content of iodine as the standard. 

Of the methods which may be used for the determination of 
the iodine there are only two which need to be considered, viz., 
the older Baumann method which consists of fusion with caustic 
alkali, liberating the iodine by suitable means from the aqueous 
solution of the fused residue, extracting it with an immiscible 
solvent, and estimating its quantity colorimetrically, and the recently 
proposed Hunter method, which differs from the above in sub- 
stituting alkali carbonates for the fusion, conversion of the iodine 
to the iodic state, and estimating its amount by a volumetric 
procedure. O'f these two methods the latter has been found by 
us to possess advantages both in reliability of the results, and 

* Read at the Boston Meeting of the American Pharmacentical Asso- 
ciation. August, igii. 

(407) 



4o8 Standard for Desiccated Thyroid ^l<iiids \^^^^:J^^^l;J'\^^^^^^^ 

convenience of execution. r\n*thennore, from the point of view 
of the Pharmacopoeia it possesses the advantage over the JUiumann 
method that no analytical procedures, volumetric solutions, or 
reagents, new to the present edition of the Pharmacopoeia, are 
required. 

In his original paper ^ Dr. Hunter gives very clear and explicit 
descriptions of all the details of the process, and there is conse- 
quently little opportunity for uncertainty in regard to any part 
of the method. It is the rule, however, in Pharmacopoeial descrip- 
tions of analytical processes, that only the essential features be 
included, consequently it appears desirable that a concise description 
of the Hunter method, in what may be called Pharmacopoeial 
language, be given. Such an outline would be as follows : 

Determination of Iodine (Hunter Method). — One gram of 
Desiccated Thyroid Gland is mixed in a nickel crucible of about 
125 c.c. capacity, with 15 grams of a mixture composed of 138 
parts by weight of anhydrous KXO.^, 106 parts anhydrous NaoCO. 
and 75 parts KNOg, and an additional 5 grams of this fusion 
mixture spread evenly over the surface. The crucible is then heated 
over a free Bunsen flame until no further carbonization is observed, 
it is cooled and the friable residue dissolved in about 150 c.c. of 
distilled HoO. To this solution contained in an Erlenmeyer flask 
of about 500 c.c. capacity, is added approximately 50 c.c, or its 
equivalent, of fresh liquor sodae chlorinatae U. S. P. (containing 
2.4 wt. per cent. CI). The mixture is then treated with enough 
phosphoric acid ( i volume of the 85 per cent, syrup and i volume 
of H2O), to produce a marked yellow tint of free chlorine, and an 
additional 10 c.c. of the phosphoric acid is then added and the con- 
tents of the flask boiled for about one-half hour or until the volume 
has been reduced to about 150 c.c. The liquid is cooled, 10 c.c. 
of I per cent, aqueous KI solution is added and the liberated 
iodine titrated with N/200 sodium thiosulphate, adding starch paste 
as the indicator just before the end of the reaction. The N/200 
thiosulphate may be made by diluting 25 c.c. of exactly N/io 
thiosulphate to 500 c.c. ; it changes strength rapidly and should 
be prepared fresh at each time determinations are made. One c.c. 
of N/200 thiosulphate corresponds to 0.0001058 gm. iodine derived 
from the sample of thyroid used. 

This method has been tested in this laboratory in comparison 

^ Hunter : Jour. Biol. Chem., 7, 321-349, 1910. 



\"piV,'mi!'}^^^^''^^'^^ f^^' Desiccated Thyroid Glands 409 

with the Bauniann method, upon quite a large number of samples 
of commercial desiccated thyroid glands. The agreements in 
duplicate determination by the Hunter method were found to be 
considerably more uniform than those by the Baumann method, 
and the results in practically every case were from 10 to 15 per 
cent, higher. Since there is a reasonable source of loss at one step 
of the Baumann method, viz., the acidification of the aqueous 
solution of the fusion residue, and this particular cause of loss has 
been obviated by Hunter in his method, there can be little doubt 
that the higher results are the nearer correct. 

Of the commercial samples which we have so far examined, 
some were purchased on the market during 1907, and the others 
recently received direct from two American firms which prepare 
thyroid glands for medicinal use. For these latter we herewith 
acknowledge our indebtedness to Armour and Co., and Parke, Davis 
and Co. The samples received direct are portions of the several lots 
prepared at the particular dates shown in the table. 

Percentage of Iodine in Commercial Desiccated Thyroid U. S. P. as 
Determined by the Hunter Method. 

Laboratory g^^^^^ Per cent. I. L^bomory g^^^^^ Percent.!. 

99 P. D. & Co. (1907) 0.185 104 Armour & Co. (1907) 0.138 

99(a) P. D. & Co. (1907) 0.185 107 Armour & Co. (1907) 0.145 

100 P. D. &Co. (1907) 0.188 108 Armour & Co. (1907) 0.138 

101 P. D. & Co. (1907) 0.153 109 Armour & Co. (1907) 0.141 

102 P. D. & Co. (1907) 0.162 109(a) Armour & Co. (1907) 0.142 

103 P. D. & Co. (1907) 0.219 119 Armour & Co. (1907) 0.135 

105 P. D. & Co. (1907) 0.138 120 Armour & Co. (1907) 0.129 

106 P. D. & Co. (1907) 0.218 121 Armour & Co. (1907) 0.140 
106(b) P. D. & Co. (1907) 0.212 

116 P. D. & Co. (1907) 0.118 Average 0.138 

117 P. D. & Co. (1907) 0.117 345 Armour & Co. Dec. 16, '09 0.279 

118 P. D. &Co. (1907) 0.158 346 Armour & Co. Jan. 23, '10 0.095 

Average 0.171 347 Armour & Co. Feb. 15, '10 0.212 

348 Armour & Co. April, '10 0.162 

358 P. D. &Co. (1911) 0.206 349 Arniour & Co. May, '10 0.146 

359 P. D. & Co. (1911) 0.206 350 Armour & Co. June, '10 0.271 

360 P. D. & Co. (1911) 0.154 351 Armour & Co. July, '10 0.202 

361 P. D. & Co. (1911) 0.214 352 Armour & Co. August, '10 0.231 

Average 0.195 353 Armour & Co. Sept., '10 0.215 

354 Armour & Co. October, '10 0.144 

355 Armour & Co. Nov., '10 0.252 

356 Armour & Co. Jan. 16, '11 0.219 

Average 0.202 

• -.1' '¥ Thyroid Proteid (Armour) 0.607 



410 Standard for Desiccated Thyroid G lands \^^'^^J^^^;J^^^^- 

From the above results it is found that the average of the 12 
P. D. & Co. samples received in 1907 is 0.171 per cent. I, while 
that for the Armour samples is 0.138 per cent. On the other hand 
the average per cents, for the recent samples are respectively 0.195 
and 0.202, thus showing that in both cases products with higher 
iodine contents are being prepared. On the whole these results 
show a very commendable degree of regularity in the percentage of 
iodine in thyroid at present on the market. With very few ex- 
ceptions none of these samples might be expected to produce a 
noticeable variation in physiological effect. There can be no doubt, 
however, that the interests of both the producer and consumer 
would be safeguarded by the establishment of a reasonable Pharma- 
copoeial standard of iodine content. Judging from the results upon 
the samples supplied by the manufacturers themselves, such a limit 
could be fixed at approximately 0.2 per cent. 1. without causing an 
undue hardship. This per cent, has already been adopted by an 
English firm. Of course sufficient latitude, of say 0.03 per cent, 
above or below this figure, should be permitted, thus making the 
extreme limits 0.17 to 0.23 per cent, iodine. 

The remaining Pharmacopoeial description which is necessary 
is that limiting the source of the raw material to certain animals 
and prescribing a reasonable limit of moisture and ash, which from 
our experiments might be placed at not exceeding 6 per cent, for 
the former and 5 per cent, for the latter, and finally the prohibition 
of all iodine in inorganic or any other form of combination than 
that peculiar to the thyroid. 

In regard to the ash content it should be mentioned that in 
general those samples with the higher percentage of iodine contain 
the lower percentage of ash, and vice versa. Thus for instance, 
of 12 samples containing more than 0.2 per cent, iodine the variation 
in the ash content was from only 3 to 4 per cent., while 6 samples 
containing approximately 0.15 per cent, iodine contained more than 
4 per cent, ash, and one sample with only 0.095 per cent, iodine 
contained more than 5 per cent, of ash. 

It has recently been suggested by certain investigators that the 
iodine of thyroid may not all be present in an equally physiologically 
active form, and consequently that it was possible by certain 
manipulative processes to remove the less active forms and retain 
the more active portion in a product which is therefore supposed to 
contain iodine in a super active condition as compared with that 



Am, Jour. Pharm. ) 
September, 1911. J 



Colorimetric Test for Caramel. 



411 



of the untreated material. A number of experiments which we 
have recently made with one of these products, designated as Thy- 
roid Proteid, have failed to confirm this hypothesis. These recent ex- 
periments indicate even more conclusively than our previous work, 
the constant behavior of the thyroid-iodine substance and the close 
relation between the iodine content and the physiological activity 
of both the desiccated thyroids and the new Thyroid Proteid. 



COLORIMETRIC TEST FOR CARAMEL.^ 
By F. a. Upsher Smith, Pharmaceutical Chemist. 

Within the past year the question of standardizing the color of 
Caramel has been engaging the attention of pharmaceutical workers. 

Dr. George A. Menge recently suggested the preparation of a 
standard solution of Caramel by boiling on a water bath for five 
minutes one-half gram of Sugar with 5 c.c. of a mixture of Sul- 
phuric Acid 2 c.c. and water 10 c.c. The resulting mixture, 
partially cooled by the addition of 25 c.c. cold water, neutralized 
with Potassium Hydroxide Solution and finally diluted to 100 c.c. 
forms the standard color with which to compare commercial samples 
of Caramel. 

The standard that I have used for several years seems to me 
to be one that is more readily applicable, as the materials are always 
on hand and the method is a simple and quick one. The method 
consists in matching a given sample of Caramel against a standard 
color consisting of a Nesslerized solution of Ammonia. For carry- 
ing out the test, make a stack solution of Ammonium Oxalate by 
dissolving .0417 gm. of Monohydrated Ammonium Oxalate, in 
crystals, in i litre of distilled water. Prepare the standard color 
by taking 10 c.c. of this stock solution, adding 38 c.c. of water and 
2 c.c. of Nessler's Solution. 

Match the standard color with the Caramel prepared as follows : 
Dissolve I gm. of the Caramel in water and make up to i litre. 
Run the solution from a burette into a Nessler glass until, on dilution 
with distilled water to 50 c.c, it exactly matches the standard color. 



. * Read before the annual Convention of the Minnesota State Pharma- 
ceutical Association, Duluth, Minn., July 12, 1911. 



412 The Fixation of Sulphide. 

As an arbitrary standard, consider the standard Caramel as one 
of which o.oi gramme (represented by lo c.c. of the diluted solu- 
tion made up to 50 c.c. with water) is required to match 50 c.c. 
of the color standard. Call this standard Caramel 100 per cent. 
Caramel as found on the market will usually test around this figure. 

To obtain the Colorimetric value of any other Caramel divide 
100 X 10 by the number of c.c. of the diluted Caramel Solution 
required. For example, in a particular test, 20 c.c. of the solution 
of the sample of Caramel were required to match the color standard. 

Then the Colorimetric value of the Caramel sample equals ^-^^ ^- = 
50 per cent. In other words, this particular sample was one-half 
strength. This strength is a convenient one for making elixirs. 

Among the advantages of this method I might mention that 
the tints of the Ammonia Solution and diluted Caramel Solution 
are practically identical. The materials for making the test are to 
be found in every laboratory and the apparatus required consists 
simply of a burette, pipettes, and two Nessler glasses. The two 
vials of liquid before you show how similar these solutions are in 
tint and illustrate the practicability of the method. This method 
is particularly valuable from the fact that it enables the operator 
to give a numerical value to any given sample of Caramel, a point 
of importance in making purchases, as well as in the manufacturing 
laboratory. 

Laboratory of Noyes Bros. & Cutler, Saint Paul, Minn. 



THE FIXATION OF SULPHIDE BY BASIC BISMUTH 
COMPOUNDS. 

By J. L. Stingel, 
From the Cleveland School o'f Pharmacy, Cleveland, O. 

In a letter to the /. A. M. A. (July 16, 1910, Vol. 55, p. 236), 
Dr. Hulse describes his experience with the so-called creams, milks 
or magmas of bismuth, in the treatment of infantile disorders, par- 
ticularly calling attention to the fact that the characteristic brown 
or black color of the stools was absent. 

At the suggestion of Prof. Sollmann, of the Western Reserve 
University Medical College, the writer made a number of experi- 



Am. Jour. Pharm. \ 
September, 1911. j 



The Fixation of Sulphide. 



413 



ments in order to determine if there were any chemical basis for 
such a difference, in other words, whether the various basic bismuth 
salts really differ in their behavior tow^ard sulphides. 

In the first series of experiments the sulphides were applied 
directly to suspensions of bismuth salts (0.5 gm. with water q.s. — 25 
cc). The reaction of the suspension to litmus paper was noted, 
through one set of samples a current of HgSwas passed to saturation. 
To the other Ammonium Sulphide (NH4)oS sol (5 cc.) was added. 



Suspensions 


Reaction 


H2S 


(NHO2S 


Bismuth Magma (dried) old 

Bismuth Magma (dried) new .... 
Bismuth Subcarbonate 

Bismuth Subnitrate 

Bismuth Subsalicylate 


Neutral 
Neutral 
Neutral 
Neutral 
Neutral 
Neutral 


Positive 
Positive 
Positive 
Positive 
Positive 
Positive 


Positive 
Positive 
Positive 
Positive 
Positive 
Positive 



Two samples of finished Creams of Bismuth, one made by the N. F. 
process, the other by Raubenheimer's modification, were tested with 
(NH^)oS; both gave dark ash colored ppts. 

It will be seen that the sulphide is formed in all, but somewhat 
less readily in the old magma. 

A second series of experiments was made to determine whether 
any bismuth goes into sol. in water. 0.5 gm. of the Bisimith subsalt 
in water q.s. 25 cc. was allowed to stand 24-48 hrs., frequently 
agitated, filtered and filtrate brought up to 25 cc. These filtrates were 
tested the same as the first series. 



Filtrates 


Reaction 


H2S 


(NH4)2S 


Bismuth Magma (dried) old 

Bismuth Magma (dried) new 

Bismuth Subcarbonate 

Bismuth Subgallate 

Bismuth Subnitrate 

Bismuth Subsalicylate 


Neutral 
Neutral 
Neutral 
Neutral 
Neutral 
Neutral 


Negative 
Negative 
Negative 
Positive 
Positive 
Negative 



Negative 

Negative 

Negative 

Positive 

Positive 

Negative 



Conclusions . — The suspensions of the various basic bismuth salts 
are practically, equally effective in binding H^S but in old magma 
this property is impaired. 

Water left in contact with the basic bismuth salts dissolves 
some bismuth from the subnitrate and subgallate but none from the 
others. 



414 Standard Suroical Dressinos. (Am jour. Pharm. 

\ September, 1911. 

STANDARD SURGICAL DRESSINGS.^ 
By Frederick B. Kilmer. 

The subject of standardization of surgical dressings was a pro- 
lific theme of discussion during a period beginning in 1893. A 
reference to the journals of that [ime will disclose the questions 
then at issue, and need not be here entered into. To understand 
the present day situation, it will be necessary to review somewhat the 
history and technic of surgical practice. 

A recent writer, Dr. Robert T. Morris, tersely sums up the 
situation as follows : 

" Surgery is now in the dawn of the fourth era. In the days 
of Hippocrates surgery was heroic. That represents the first era. 
Then came Vesalius and the anatomists, and we had the second or 
anatomic era. Pasteur and Lister introduced the third, or the patho- 
logic era. While this third, or pathologic era, is now prevailing 
to a great extent, it is rapidly passing to what this authority named 
as the fourth or physiological era." 

The dominant idea of this fourth era is to prevent the develop- 
ment of bacteria in wounds, and to remove the products of infection 
by means of the art. The present day surgical dressing has been 
evolved out of the Listerian era. Peculiar to the Listerian era, 
especially in its opening period, was the use of antiseptics, which 
were applied in the form of sprays, irrigation, washing and the like. 

Lister devised a series of dressings made by combining an anti- 
septic, chiefly carbolic acid, with resins and parafiin, somewhat 
resembling a cerate or plaster mass ; this was poured while hot into 
meshes of lint, afterwards upon gauze cloth. The intention of this 
dressing was that the gauze should adhere to the flesh and that 
the vehicle or cloth should prevent the volatilization of the carbolic 
acid. Very quickly it was found more convenient to take a piece of 
gauze or cotton and dip it into antiseptic solutions such as were then 
in use. 

The National Formulary of this period contained a formula 
for carbolized gauze, essentially an adhesive mass containing carboHc 
acid. The Formulary at this time adopted as a standard of fabric, 
a market gauze known as Lehigh E. 

It is perhaps interesting to note that the amount and strength 

^ Read at the meeting of the New Jersey Pharmaceutical Association, 
June 14, 1911. 



Am. Jour. Pharm.) 
September, 1911. J 



Standard Surgical Dressings. 



415 



of the antiseptics used at this time were markedly different from 
these in use to-day. For example, we find at this time acid used 
in a strength of i in 12, i in 20; corrosive sublimate 1-200, and 
iodoform 20 per cent. 

The method of preparing" iodoform gauze in the practice of the 
originators may be mentioned : Iodoform was first used by dusting 
directly over the wound. Bilroth afterwards stated that when the 
iodoform was dusted over the fibre of cloth it was less irritating 
than when applied directly to the wound, and he later adopted a 
dressing containing 20 per cent, iodoform. 

A feature of this period was the English practice of using 
boracic acid in a strength as high as 40 per cent. It is stated that 
this was fostered by the producers because the dressings were sold by 
the pound, and boracic acid was much cheaper than the fabric. 

This was only twO' decades ago. Now we find that carbolic acid, 
the agent which helped in the revolution of the world of surgery in 
the time of Lister, has passed into disuse in surgical technic; that 
the strength of corrosive sublimate, and its preparations, has be- 
come weaker and weaker until there is now demanded a strength of 
1-10,000 ; that iodoform has shrunk from, a strength of 40 per cent, 
to 2 per cent. ; and that many antiseptics once in very large 
demand and for which much was claimed have been forgotten. 

In the later days of the third era of surgery and in the opening 
of the fourth era, antiseptic surgical dressings have been but little 
used. The demand is now for sterilized cotton, sterilized gauze, 
sterilized bandages. If antiseptics are used they are applied in 
certain classes of cases and as an adjunct — not as an important part 
of the technic. The surgeons are learning the value of procedures 
briefly characterized as " skilful neglect " ; they are learning that 
antiseptics even in a weak solution are damaging to the growth 
of new tissue ; that sterilized water produces untoward results ; 
and that the much lauded hydrogen peroxide is destructive. Some 
go so far as to claim that cotton or gauze placed ever so gently 
upon a surface undergoing cell repair is harmful, because new 
cells are caught in the fibrous mesh and torn away when the dressing 
is changed. 

All that is necessary, is a protection medium. At best in the 
present day practice we have tO' consider only plain absorbent gauze 
cloth in its various forms, such as bandages, tapes, etc., and ab- 
sorbent cotton. These two substances represent almost entirely the 
surgical dressing of the period. 



4i6 



Standard Surgical Dressings. 



JAm. Jour. I'harui. 
I Septt-mlKM-, lyU. 



In view of the facts cited, and for other reasons which might 
be urged, it would seem to me to be a useless proceeding for either 
the Pharmacopoeia or the National Formulary to attempt to standard- 
ize surgical dressings, especially those of the antiseptic or medicated 
type. 

It will readily be seen that in the period covered by the Eighth 
Revision of the Pharmacopoeia, this type of dressings has radically 
changed, and for the most part has gone out of existence, and unless 
the Pharmacopoeia and the National Fonuulary are revised much 
more rapidly than has been the case in the past, any such standard- 
ization would become obsolete soon after its publication. Antiseptic 
dressings are the relics of a rapidly changing practice — an era of 
surgery which has passed, and thus for the druggist, belong to a 
declining trade. 

As of some slight interest we may here insert a table prepared 
sometime ago by one of the manufacturers of surgical dressings, 
which was intended to show the consumption of surgical dressings 
made of cotton. It is as follows : 



Cotton Used in Surgery in the United States. 





1878 


1886 


1898 


1910 


Raw cotton (lb.) 


1,000 


5,000 


20,000 


25,000 




t:,ooo 


250,000 


3,000,000 


5,000,000 


Bandages (lb.) 


10,000 


20,000 


100,000 


200,000 


Gauze (yds.) 


1,200 


120,000 


20,000,000 


50,000,000 


Lint (lb.) 


50,000 


45,000 


40,000 


40,000 


Miscellaneous dressings (lb.) 


500 


2,000 


20,000 





While the consumption of antiseptic dressings was not enumer- 
ated in the table, it may be stated that in the face of this enormous 
increase in certain types, antiseptic dressings have steadily and 
rapidly declined, until some of them have gone out of existence. 
As an example of these which have almost entirely disappeared we 
may instance salicylated acid cotton, styptic cotton, iodized cotton, 
iodoform cotton, Lister's cyanide of mercury and zinc gauze, and 
salalembroth cotton and gauze. 

Various formulas for antiseptic cottons and gauzes may be 
found in the British Pharmaceutical Codex, the French Codex, and 
Dcitricirs Pharmazcutisches Manuel, and other works to which the 



Am. Jour. Pharm. I 

September, 1911. ) 



Standard Surgical Dressings. 



417 



reader is referred. They need not be discussed except briefly to 
call attention to some of the formulas given in the British Pharma- 
ceutical Codex, where, under the head of Carbolized Cotton, attention 
is called to the fact that the preparation soon loses strength by 
exposure ; it is only of approximate strength when freshly made. 

In certain instances, in capsicum cotton and mercuric iodide cot- 
ton, it is recommended that the cotton be dyed in order that it may 
appear to the eye as of normal strength. In the case of corrosive 
sublimate cotton the statement is made that this soon deteriorates. 
In the case of carbolic acid gauze, cyanide gauze, and iodoform 
gauze — it is noted in the Codex that they undergo rapid change — 
and in the case of corrosive sublimate it is stated that the mercuric 
chloride undergoes decomposition in a month or six weeks. 

These statements from an official authority would indicate that 
it would be difficult to formulate an absolute standard to be embodied 
in a Pharmacopoeia, the legal authority by which preparations named 
therein shall be judged. In other words, a given antiseptic gauze, 
prepared exactly according to the official formula, would not and 
could not retain its conformity to the standard, and were the sug- 
gestions embodied in a most excellent paper by Geo. M. Beringer, 
Jr., American Journal of Pharmacy, April, 191 1, where formulas 
for the preparation of antiseptic gauze dressings are given, with 
the further addition of a process for sterilization by steam, dry heat, 
etc., adopted, the difficulty would be greatly increased. Mr. Berin- 
ger evidently fails to take into account the fact that his process of 
sterilization when applied to such preparations as iodoform, thymol, 
carbolic acid, and other volatile substances, would bring about a 
complete change in the product, so that the finished article is not 
what it started to be. 

In the early days of the Listerian or antiseptic era of surgery, 
it was a common custom for the surgeon to prepare his own gauze 
at the operating table or bedside of the patient. This he did by 
simply dipping the gauze or cotton into a solution of a given 
strength and apply it direct to the wound, and this practice applies 
to a certain extent to-day as an emergency practice, except that 
the strength of the antiseptic solutions has been greatly modified. 

It is my judgment that the pharmacist will only be called upon 
to prepare antiseptic dressings in extreme cases. Even in emer- 
gency practice, plain, sterile gauze or cotton is considered adequate. 
When we take up the question of plain dressings, such as cotton 



4i8 



Standard Surgical Dressings. 



( Am. Jour. Pharm. 
( Sei)teml)fr, 1911. 



or gauze not impregnated with an antiseptic, there is possibly an 
opportunity for the Pharmacopoeia or the National Formulary to 
establish certain standards. 

I have discussed this question at some length (Journal of the 
Society of Chemical Industry, October 31, T904). Here 1 have 
called attention to the fact that the Pharmacopieial standards thus 
noted were open for criticism. 

In respect to the standards of the United States Pharmacopoeia, 
among its faults are the tests for absorbency. Absorbent cotton, 
even when heavily charged with impurities, will, when pressed in 
the hand and placed on the surface of water, sink. The Pharmaco- 
poeia is very indefinite as to the amount of water to be used. The 
United States Pharmacopoeia has it that, when purified cotton, 
previously pressed in the hand, is placed on the surface of cold water, 
it will absorb the water and sink, and the water should not acquire 
an acid or alkaline reaction. 

The test of sinking in water is a test neither of purity nor absorb- 
ing power. Soap or glycerine will increase the apparent absorbency. 

• The following has been suggested by me as a more rational 
Pharmacopoeial standard for puiified or absorbent cotton, and these 
standards are those to which the leading brands now on the market 
will be found to comply. In other words, they are standards which 
are attainable, and which will exclude cottons of a low grade or to 
which foreign substances have been added : 

GossYPiuM Purification. 
Purified Cotton. 

Suggested Standard. — The hairs of the seed of Gossypium 
(Fam. Malvaceoe) freed from adhering impurities and deprived 
of fatty matter. 

White, soft, fine filaments, appearing under the microscope as 
hollow, flattened and twisted bands, spirally striate, and slightly 
thickened at the edges ; inodorous and tasteless ; insoluble in ordinary 
solvents, but soluble in an ammoniacal solution of cupric oxide. 

When purified cotton, previously compressed in the hand, is 
thrown on the surface of cold water, it should readily absorb the 
latter and sink. 



Am. Jour, riiarm. 1 
September, 1911. J 



Standard Surgical Dressings. 



419 



Purified cotton should contain no more than a very small quan- 
tity, if any, of visible impurities, and on combustion of five grammes 
or more should not leave more than 0.2 per cent, of ash. 

Ten grammes of purified cotton are saturated with 100 c.c. 
neutral distilled water, the water pressed out and divided into two 
portions, each of which is placed in a white porcelain dish. To 
one portion is added 3 drops phenolphthalein T. S., and to the 
other portion one drop methyl orange T. S. Neither portion should 
develop a pink color (absence of acid or alkaU). 

If 20 grammes be extracted in a narrow percolator with ether 
until 300 c.c. percolate is secured, the percolate should on evaporation 
to dryness in a tared beaker leave a residue of not more than 
0.5 per cent, of the weight of cotton used (limit of fatty matter). 
A blank test should be made with an equal quantity of the ether used. 

If 20 grammes be extracted in a narrow percolator with alcohol 
until 200 c.c. percolate is secured, the percolate should not be of 
a blue or green tint (absence of dyes) and on evaporation to dryness 
in a tared beaker the residue should amount to not more than 0.5 
per cent, of the cotton used (limit of resins and soap). A blank 
test should be made with an equal quantity of the alcohol used. 

If 20 grammes be extracted in a narrow percolator with hot 
distilled water (80° to 90° C.) until 200 percolate is secured, the 
percolate should not be clouded (absence of soap), and on evapora- 
tion to dryness in a tared beaker the residue should amount to not 
more than 0.2 per cent, of the weight of cotton used (limit of soluble 
salts). A blank test should be made with an equal quantity of the 
water used. 

Gauze cloth, otherwise known as surgical gauze, came into use 
as a wound dressing with Listerism. Lister first applied lint, after- 
wards what was known as cheese cloth, which by evolution, was 
converted into surgical gauze, and finally a combination of absorbent 
gauze and cotton. The tendency of modern surgical technic has 
been to simplify dressings. All other substances have to a . large 
extent been abandoned and gauze made to constitute almost solely 
the dressing material. 

A good quality gauze has numerous and obvious advantages over 
any other material for this purpose. It is highly absorbent, pliable, 
with an open texture that is firm and strong, it is free from the 
loose fibres and irritating particles found in unspun cotton. It 
is cool, light, and readily shaped into required forms. 



420 



Standard Surgical Dressiiigs. 



f Am, Jour. Pharm. 

\ .SeiJteiuber, 1911. 



Surgical gauze in the operating room acts primarily as a cover- 
ing and protective, and if of sufficient thickness filters the external 
air that passes through to the wound. It is hrm enough to hring 
together any incised or separated parts, its fihres act, to a certain 
extent, as plugs or compressors to the small blood-vessels which 
may have been severed. The absorptive power of good gauze is 
ample to receive and retain a sufficient quantity of blood to coagu- 
late and coat the injured part and thereby check the flow. 

Gauze is also employed to absorb discharges which would infect 
the surrounding area if not seized upon by an absorbent and re- 
moved. In the early technic antiseptics of disinfectants were used 
to impregnate gauze dressings. In modern surgery a piece of 
sterile gauze is sometimes the only dressing employed. 

Taken altogether surgical gauze may be considered the most 
convenient and the most useful dressing material now known. 

Gauze cloth in the cotton trade is known as "Cheese Cloth," 
" Tobacco Cloth," or unbleached gauze, and it is quite distinct from 
surgical gauze, although large quantities of the former are used for 
surgical purposes. In England and on the Continent gauze is spun 
and woven solely for surgical uses, and there is one such maker 
in the United States. 

The method of preparing cotton fibre for manufacture into sur- 
gical gauze is described in the paper heretofore cited, and consists 
of a long series of mechanical and chemical processes, a description 
of which lies outside of our present purpose. 

In the surgical gauzes as found on the market there is a marked 
variation in the length of the fibre, the size and weight of the thread, 
yardage per pound, and other physical and chemical characteristics. 
The earlier surgical gauzes were made of Egyptian cotton, carried 
an equal number of threads each way, and were hand-finished. The 
hand-finish process kept the thread straight, the final product was 
less white, but more elastic. 

In some samples of gauze in our market there will be found 
certain dressings or loadings added to improve appearance, to in- 
crease the weight, to assist in holding the gauze out to its full width, 
and the like. 

In the cotton trade, gauze and cloths of this character are 
standardized by taking a square and counting the number of threads 
per square inch. For example, a high-grade gauze carrying forty 
longitudinal and forty-four cross threads per square inch, carried 
eighty-four inches of thread. 



Am. Jour. Pharm. ) 
September, 1911. J 



Standard Surgical Dressings. 



421 



For the most part the so-called manufacturers of surgical gauze 
purchase their supplies of woven gauze, gray or bleached, from 
the various mills of New England. These mills supply some nine- 
teen grades, beginning with a gauze carrying twenty threads by 
ten, or thirty threads per square inch. 

It should be noted that very little if any surgical gauze in the 
market is fully thirty-six inches in width. This is accounted for 
by the fact that these goods are woven in the gray thirty-six inches 
wide, and it is not practicable to bleach the goods, render them 
absorbent, and retain their full width. The usual variation is 
about one inch per yard ; in other words, the average width will be 
found to be about thirty-five inches. 

The following table shows the threads per inch, the average 
yardage per pound of the best known grades of surgical gauze : 



Surgical Gauze. 

Threads per inch. Yards per pound. 

44 X 40 9-38 

32x36 ' 14.81 

28 X 24 16.00 

24 X 20 18.83 

20 X 14 23.20 



The National Formulary (First Edition), adopted as a standard 
two brands, Lehigh E. and Stillwater. These grades (now practi- 
cally out of market) contained about sixty-four threads per square 
inch, and their weight was a little less than 800 grains to the square 
yard. 

The nearest approach to a standardization of plain surgical 
gauze is one which I understand has been adopted by the Bureau 
of Municipal Research, which bureau is making an attempt to 
secure uniformity in the supplies for the various departments of 
New York City. 

In respect to gauze the requirements are that the gauze shall 
count in the finished state not less tiian the total number of threads 
per square inch specified, shall not exceed the yardage per pound 
specified ; it shall be free from loading, and shall be acceptable 
by the bureau as first quality in every respect. Gauze delivered 
under these specifications is required to be made from clean, white, 



422 Standard Suri>ical Dressings. (Am. jour. Phaim. 

^ ( September, 1911. 

long cotton fibre, fully bleached and absorbent, of soft finish, and 
upon extraction with acidulated water (two' per cent, hydrochloric 
acid) of not more than one per cent residue, and the reaction shall 
show no reaction for starch, soap, dextrin, glue or other filling. 

The object of the foregoing test — extraction with acidulated 
water — is to prevent the addition of starch, soap, dextrin, or glue 
for making weight, increasing the apparent size of thread, etc. 

This requirement would seem to be about as far as any standard 
could be expected to reach ; indeed, the great variation in the require- 
ments of the surgeon and the manifold mechanical household 
uses of gauze create a legitimate demand for a greatly varying 
material. 

Mr. Geo. M. Beringer, Jr., in a paper heretofore cited, raises 
the question as to whether the Pharmacopoeial recognition of medi- 
cated gauzes and surgical dressings would be a mistake. He 
states that it has been hinted that the pharmacist has not the facili- 
ties and training necessary for the preparation of surgical dress- 
ings, and he urges that this arraignment is not complimentary to the 
intelligence of the American pharmacist. He calls attention to the 
fact that the pharmacists of Germany, Austria, Sweden, Belgium, 
and elsewhere prepare such preparations from formulas in their 
respective pharmacopoeias. 

To my mind there is no question but that the pharmacist has the 
intelligence and perhaps the training necessary for the careful prep- 
aration of surgical dressings. It is not a question of can he, but will 
he take the care to properly prepare these dressings. 

I have discussed this question at some length in a previous paper, 
in which the question was raised as to the relative fitness of the sur- 
geon, the pharmacist and the manufacturer as makers and purveyors 
of surgical material. In this paper I stated that we may well claim 
for the American physician the highest of honors, we should all 
reverence the skill and genius of the American surgeon, yet it 
must be admitted that their offices are not as a rule the most suitable 
spot for the preparation of dressings. Contact with the clothing 
and person of patients carrying contagion of every name and kind, 
together with a thousand and one avenues through which the 
streams of infection may pour into their rooms, is evidence of the 
unfitness of the surroundings of the physician for the preparation 
of surgically clean dressings. 

Likewise in hospitals, many of which are attached to medical 



Am. Jour. Pharm. ( 
September, 1911. J 



Standard Surgical Dressings. 



423 



colleges, where students and operators carry infection from hun- 
dreds of sources of contagion, and where the dangers of infection 
can scarcely be avoided. 

When dressings are prepared by the pharmacist the work is of 
necessity performed in the druggist's back room — a place which 
comes far short of conditions known as surgical cleanliness. The 
pharmacist, though ordinarily clean in person and habits in the 
pursuit of his calling, is far from aseptic. Like the physician, 
he is constantly in contact with infection through the person of his 
patrons. 

In a few terse sentences Mr. Beringer attempts tO' convert the 
druggist's work table into a room suitable for the preparation of 
aseptic dressings. I doubt his ability, or the ability of the average 
pharmacist, to take these products into his own back room and 
produce therefrom sterile dressings. In advance, I would acknowl- 
edge my own inability to do so, notwithstanding a generation of 
experience along these lines, and should the necessity arise for an 
important operation in my own case, I certainly would reject dress- 
ings prepared either in a hospital, a physician's office, or the pharma- 
cist's back room in favor of these made by a reliable manufacturer. 

The facilities of the manufacturer whose whole organization is 
adapted to the production of surgical dressings are certainly more 
perfect than those of the surgeon to whorh such work is only inci- 
dental ; the employment of a room from which pathogenic organisms 
are entirely excluded is superior to the conditions in the hospital 
or doctor's office. Rooms in which no work is undertaken except the 
handling of aseptic material will certainly be more nearly surgically 
clean than a place where infection has constant access. Persons 
whose only calling is that of preparing surgical material, who have 
been trained in the principles underlying the disinfection of dress- 
ings, are much more competent to handle the same than the doctor's 
assistant to whom such work is of necessity relegated. Further, an 
organization devoted exclusively to the manufacture of dressings, 
once having the table arranged to prepare a yard of dressing, can 
produce any number of yards more perfectly than if done as 
occasion may require. 

To the manufacturer and the dispensing pharmacist is due the 
credit of having made possible the convenient application of the 
principles of modern surgery. 



424 



Standard Surgical Pressings. 



j All). Jour. Pliarin. 
\ S.'iJtciiit.ci, 1911. 



Conclusion. 

A summary of the thoughts embraced in the foreg-oing paper 
is as follows : 

The rapidly changing conditions of surgical, methods would not 
seem to warrant the insertion in the United States Pharmacopoeia or 
in the National Formulary formula for the preparation of antiseptic 
surgical dressings. Any standard adopted for medication for sur- 
gical dressings would be liable to become valueless long before 
the next revision. A standard for antiseptic dressings once em- 
bodied in the Pharmacopoeia would become complicated in the 
administration of food and drug laws by the constantly changing 
requirements of surgical practice. 

It might be possible to establish official methods of assay by 
which antiseptic dressings could be judged. The standard for 
absorbent cotton in the eighth revision of the United States Pharma- 
copoeia should be revised, and a standard is suggested herein. It 
would be possible to establish a standard by which surgical gauze 
and dressings made therefrom could be judged. 

The principal requirements for surgical dressings made of cotton 
or gauze at the present time are purity and sterility ; such dressings 
are known as plain aseptic dressings. 

In the author's opinion, neither the facilities of the practicing 
physician, the hospital, nor those of the ordinary pharmacist are 
adequate for the preparation of dressings to meet modern require- 
ments. The preparation of this class of material, like that of 
serums, toxins, and the like, recjuires special training and special 
facilities for their manufacture. Until economic conditions shall 
greatly change it is the author's opinion that the preparation of this 
class of material had best be relegated to those possessing the 
required facilities. 



Am, Jour. I'barm. ) 
September.^iyil. J 



Queries on Alkaloidal Assay. 



425 



SOME QUERIES ON ALKALOIDAL ASSAY. 
By W. a. Pearson, Philadelphia. 

Much good work has been recently presented on alkaloidal 
assay, and it is reasonable to expect that much more satisfactory 
and accurate methods will be inserted in the next Pharmacopoeia 
of the United States. 

There are a few differences of opinion in regard to technic, 
however, that should be agreed upon before uniformity is to be 
expected. 

Amount of Moisture in Drug. — Crude drugs are not as a rule 
assayed in the exact condition in which they are received. Fre- 
quently they must be dried before they can be ground and this loss 
of water may amount to as much as 30 per cent. Is it advisable 
to compute the results obtained to correspond to the original con- 
dition of the drug or to the moisture free basis? 

Fineness of Powder. — It is well known that when a powder is 
ground^ all of the particles are not of equal size and that if all the 
drug is ground and only the particles of a certain size are taken 
the sample will not be a representative one. 

Would it therefore be advisable instead of stating that the 
powder should be of a certain fineness to state that it should be 
at least of a certain fineness or between certain limits of fineness? 

Temperature. — In certain alkaloidal determinations the tem- 
perature plays an important part, in the results obtained. For 
example, in the assay of opium, the crystallization flask is directed 
to be set aside in a moderately cool place. No limits are given in 
U. S. P. for moderately cool " and this temperature has been 
variously interpreted by different analysts. It is certain that much 
larger crystals are obtained near 0° C. than at slightly higher 
temperatures ; it therefore seems important to ask what influence 
does temperature have upon the results of an alkaloidal assay? 

Fumes. — Free alkaloids very readily combine with acids, and 
the analytical laboratory usually contains fumes of hydrochloric 
or nitric acids. Before the delicate titration of an alkaloidal residue 
is made there seems to be danger of these fumes combining with 
the alkaloid and lowering the results. To what extent do the 
fumes ordinarily present in the laboratory influence the results of 
an alkaloidal assay? 

Indicators. — It has been claimed by the analysts in one lab- 



426 



Queries on Alkaloidal Assay. 



f Am. Jour. Pharm. 
\ September, 1911. 



oratory that cochineal is the best indicator for all alkaloidal titra- 
tions ; the men in another laboratory prefer the general use of 
iodeosin. Does the indiscriminate use of these indicators give con- 
cordant results and would the assay be considered as being made 
according to the U. S. P. if an indicator not specified in the particular 
assay were used in the titration? 

Color of End Point. — In all the alkaloidal titrations, the U. S. P. 
specifies that the standard solution should be added until a certain 
color is obtained. Owing to differences in judging the end point 
and the absence of a definite color standard a considerable variation 
is to be expected. 

Ought not the end point of an alkaloidal titration be determined 
by matching a certain color of a standard chart under definite 
conditions ? 

Blank Determinations. — To avoid the difficulty of judging the 
color of the end point and to provide a check on the solutions 
being used a blank determination is usually made by the most 
analysts. Even this method is faulty where the alkaloidal residue 
still retains some color. Would it be advisable to specify that a 
blank test be made with every alkaloidal titration ? 

Amount of Solvent. — Most practical analysts who are regularly 
making alkaloidal assays are agreed that insufficient solvents are 
specified for extraction of alkaloids in many of the U. S. P. processes. 
For example, in the assay of Nux Vomica after oxidation of the 
Brucine the quantity of chloroform specified will not leave the 
supernate liquid clear nor will twice the specified quantity